DNA minor groove binders as potential antitumor and antimicrobial agents

Medicinal Research Reviews

Volumn 24, Issue 4, 2004, Pages 475-528

  Baraldi, Pier Giovanni ^a   Bovero, Andrea ^a   Fruttarolo, Francesca ^a   Preti, Delia ^a   Tabrizi, Mojgan Aghazadeh ^a   Pavani, Maria Giovanna ^a   Romagnoli, Romeo ^a  

^a UNIVERSITY OF FERRARA   (Italy)

Author keywords

Clinical evaluation; DNA; Hybrid molecules; Minor groove binders

Indexed keywords

1,2,3,11A TETRAHYDRO 8 HYDROXY 7 METHOXY 5H PYRROLO[2,1 C][1,4]BENZODIAZEPIN 5 ONE; 2,5 BIS(4 AMIDINOPHENYL)FURAN; 4 [5 (4 METHYL 1 PIPERAZINYL)[2,5' BI 1H BENZIMIDAZOL] 2' YL]PHENOL; 4 CHLOROMETHYL 1,4,5,6 TETRAHYDRO 6 [5 [(7 METHOXYBENZOFURAN 2 YLCARBONYL)AMINO] 1H INDOL 2 YLCARBONYL] 8 [(4 METHYL 1 PIPERAZINYLCARBONYL)OXY] 2 TRIFLUOROMETHYLPYRROLO[3,2 E]INDOLE 3 CARBOXYLIC ACID METHYL ESTER; 4',6 DIAMIDINO 2 PHENYLINDOLE; ADOZELESIN; ANTHRAMYCIN; ANTIINFECTIVE AGENT; ANTINEOPLASTIC AGENT; AROMATIC AMIDE; AT 760; BENZIMIDAZOLE DERIVATIVE; BENZODIAZEPINE DERIVATIVE; BIZELESIN; CARZELESIN; DIMINAZENE ACETURATE; DISTAMYCIN A; DU 86; FURAN DERIVATIVE; HOE 33342; HOECHST 33377; PENTAMIDINE; PIBROZELESIN; PNU 157911; PNU 160366; PNU 193821; POROTHRAMYCIN; RACHELMYCIN; SYBIROMYCIN; TOMAMYCIN; TRABECTEDIN; U 71184; UNCLASSIFIED DRUG; UNINDEXED DRUG; UTA 6026;

ANTIMICROBIAL ACTIVITY; ANTINEOPLASTIC ACTIVITY; BINDING AFFINITY; BONE MARROW DEPRESSION; BONE MARROW SUPPRESSION; BONE MARROW TOXICITY; CARDIOTOXICITY; COMPLEX FORMATION; DRUG CYTOTOXICITY; DRUG DNA BINDING; DRUG MECHANISM; DRUG POTENCY; DRUG SELECTIVITY; GASTROINTESTINAL TOXICITY; HUMAN; HUMAN CELL; LEUKOPENIA; LIVER TOXICITY; NEPHROTOXICITY; NONHUMAN; RAT; REVIEW; SIDE EFFECT; STEREOSPECIFICITY; THROMBOCYTOPENIA;

ANTI-INFECTIVE AGENTS; ANTINEOPLASTIC AGENTS; DNA; HUMANS;

EID: 3042662220     PISSN: 01986325     EISSN: None     Source Type: Journal    
DOI: 10.1002/med.20000     Document Type: Review

References (245)

1. Dann O, Fernbach R, Pfeifer W, Demant E, Bergen G, Lang S, Lurding G. Trypanocidal diamidines with three ring in two isolated ring systems. Just Lieb Ann Chem 1972;760:37-87.
2. Chandra P, Mildner B, Dann O, Metz A. Influence of 4′-6′- diamidino-2-phenylindole on the secondary structure and template activities of DNA and polydeoxynucleotides. Mol Cel Biochem 1977;18:81-86.
3. Mildner B, Metz A, Chandra P. Interaction of 4′-6′-diamidino- 2-phenylindole to nucleic acids, and its implication to their template activity in RNA-polymerase reaction of E. Coli bacteria and of Friend-virus infected mouse spleen. Cancer Letters 1978;4:89-98.
4. Zimmer C, Wahnert U. Non-intercalating DNA-binding ligands: Specificity of the interaction and their use as tools in biophysical, biochemical and biological investigations of the genetical material. Prog Biophys Mol Biol 1986;47:31-112.
5. Larsen T, Goodsell DS, Cascio D, Grzeskowiak K, Dicherson RE. The structure of DAPI bound to DNA. J Biol Struct Dyn 1989;7:477-491.
6. Jensch H. 4,4′-Diamidinodiazoaminobenzene, a new remedy against Trypanosoma and Babesia infections. Arzneimittel-Forsch 1955;5:634-635.
7. Newton BA. Berenil, a trypanocide with selective activity against extranuclear DNA. Antibiotics 1975;3: 34-47.
8. Newton BA, Le Page RWF. Preferential inhibition of extranuclear deoxyribonucleic acid synthesis by the trypanosome berenil. Proc Biochem Soc 1967;105:50P.
9. Wierenga W. Sequence-selective DNA-interactive antitumor agents. Drugs of the Future 1991;16:741-750.
10. Yoshida M, Banville DL, Shafer RH. Structural analysis of d(GCAATTGC)2 and its complex with berenil by nuclear magnetic resonance spectroscopy. Biochemistry 1990;29:6585-6592.
11. Queener SF. New drug developments for opportunistic infections in immunosuppressed patients: Pneumocystis carinii. J Med Chem 1995;38:4739-4759.
12. Nunn CM, Neidle S. Sequence-dependent drug binding to the minor groove of DNA: Crystal structure of the DNA dodecamer d(CGCAAATTTGCG)2 complexed with propamidine. J Med Chem 1995;38:2317-2325.
13. Nguyen B, Lee MPH, Hamelberg D, Joubert A, Bailly C, Brun R, Neidle S, Wilson WD. Strong binding in the DNA minor groove by an aromatic diamidine with a shape that does not match the curvature of the groove. J Am Chem Soc 2002;124:13680-13681.
14. Donkor IO, Tidwell RR, Jones SK. Pentamidine congeners. 2. 2-Butene-bridged aromatic diamidines and diimidazolines as potential anti-Pneumocystis carinii pneumonia agents. J Med Chem 1994;37: 4554-4557.
15. Tidwell RR, Jones SK, Geratz JD, Ohemeng KA, Cory M, Hall JE. Analogs of 1,5-bis(4-amidophenoxy)pentane (pentamidine) in the treatment of experimental Pneumocystis pneumonia. J Med Chem 1990;33:1252-1257.
16. Huang TL, Zhang Q, White AT, Queener SF, Bartlett MS, Smith JW, Donkor IO. Synthesis and anti-Pneumocystis carinii activity of piperidine-linked aromatic diimidazolines. Bioorg Med Chem Lett 1996; 17:2087-2090.
17. Tao B, Huang TL, Zhang Q, Jackson L, Queener SF, Donkor IO. Synthesis and anti-Pneumocystis carinii activity of conformationally restricted analogues of pentamidine. Eur J Med Chem 1999;34:531-538.
18. Huang TL, Tao B, Quarshie Y, Queener SF, Donkor IO. N,N′-bis(4-(N- alkylamidino)phenyl)homopiperazines as anti-Pneumocystis carinii agents. Bioorg Med Chem Lett 2001;11:2679-2681.
19. Boykin DW, Kumar A, Xiao G, Wilson WD, Bender BC, Mc Curdy DR, Hall JE, Tidwell RR. 2,5-Bis(4-(N-alkylamidino)phenyl)furans as anti-Pneumocystis carinii agents. J Med Chem 1998;41:124-129.
20. Das BP, Boykin DW. Synthesis and antiprotozoal activity of 2,5-bis(4-guanylphenyl)furans. J Med Chem 1977;20:531-536.
21. Steck EA, Kinnamon KK, Davidson DE, Duxbury RE, Johnson AJ, Masters RE. Trypanosoma rhodesience. Evaluation of the antitrypanosomal action of 2,5-bis(4-guanylphenyl)furan dihydrochloride. Exp Parasitol 1982;53:133-144.
22. Boykin DW, Kumar A, Spykala J, Zhou M, Lombardy RJ, Wilson WD, Dykstra CC, Jones SK, Hall JE, Tidwell RR, Laughton C, Nunn CM, Neidle S. Dicationic diarylfurans as anti-Pneumocystis carinii agents. J Med Chem 1995;38:912-916.
23. Neidle S, Kelland LR, Trent JO, Simpson IJ, Boykin DW, Kumar A, Wilson WD. Cytotoxicity of bis (phenylamidinium)furan alkyl derivatives in human tumor cell lines: Relation to DNA minor groove binding. Bioorg Med Chem Lett 1997;7:1403-1408.
24. Simpson IJ, Lee M, Kumar A, Boykin DW, Neidle S. DNA minor groove interactions and biological activity of 2,5-bis (4-(N-alkylamidino) phenyl)furans. Bioorg Med Chem Lett 2000;10:2593-2597.
25. Francesconi I, Wilson WD, Tanious FA, Hall JE, Bender BC, Tidwell RR, Mc Curdy D, Boykin DW. 2,4-Diphenyl furan diamidines as novel anti-Pneumocystis carinii pnemonia agents. J Med Chem 1999;42: 2260-2265.
26. Del Poeta M, Schell WA, Dykstra CC, Jones S, Tidwell RR, Czarny A, Bajic M, Kumar A, Boykin DW, Perfect JR. Structure-in vitro activity relationships of pentamidine analogues and dicationic-substituted bis-benzimidazoles as new antifungal agents. Antimicrob Agents Chemother 1998;42:2495-2502.
27. Stephens CE, Tanious F, Kim S, Wilson WD, Schell WA, Perfect JR, Franzblau SG, Boykin DW. Diguanidinoand "reversed" diamidino 2,5-diarylfurans as antimicrobial agents. J Med Chem 2001;44: 1741-1748.
28. Hopkins KT, Wilson WD, Bender BC, Mc Curdy DR, Hall JE, Tidwell RR, Kumar A, Bajic M, Boykin DW. Extended aromatic furan amidino derivatives as anti-Pneumocystis carinii agents. J Med Chem 1998; 41:3872-3878.
29. Bailly C, Tardy C, Wang L, Armitage B, Hopkins K, Kumar A, Schuster GB, Boykin DW, Wilson WD. Recognition of AGTA sequences by the unfused aromatic dication DB293 forming stacked dimers in the DNA minor groove. Biochemistry 2001;40:9770-9779.
30. Lansiaux A, Dassonneville L, Facomprè M, Kumar A, Stephens CE, Bajic M, Tanious F, Wilson WD, Boykin DW, Baiily C. Distribution of furamidine analogues in tumor cells: Influence of the number of positive charges. J Med Chem 2002;45:1994-2002.
31. Harshman KD, Dervan PB. Molecular Recognition of B-DNA by Hoechst 33258. Nucleic Acids Res 1985;13:4825-4835.
32. Gravatt GL, Buguley BC, Wilson RW, Denny WA. DNA-directed alkylating agents. 6. Synthesis and antitumor activity of DNA minor groove-targeted aniline mustard analogues of pibenzimol (Hoechst 33258). J Med Chem 1994;37:4338-4345.
33. Reddy BSP, Sharma SK, Lown JW. Recent developments in sequence selective minor groove DNA effectors. Curr Med Chem 2001;8:475-508.
34. Ji Y-H, Bur D, Häsler W, Runtz Schmitt V, Dorn A, Bailly C, Waring MJ, Hochstrasser R, Leupin W. Trisbenzimidazole derivatives: Design, synthesis and DNA sequence recognition. Bioorg Med Chem 2001;9: 2905-2919.
35. Czarny A, Boykin D, Wood AA, Nunn CM, Neidle S, Zhao N, Wilson WD. Analysis of van der Waals and electrostatic contributions in the interactions of minor-groove binding benzimidazoles with DNA. J Am Chem Soc 1995;117:4716-4717.
36. Bontemps J, Houssier C, Fredericq E. Physico-chemical study of the complexes of 33258 Hoechst with DNA and nucleohistone. Nucleic Acids Res 1975;2:971-984.
37. Loontiens FG, Regenfuss P, Zechal A, Dumortier L, Clegg RM. Binding characteristics of Hoechst 33258 with calf thymus DNA, poly [d(A-T)], and d (CCGGAATTCCGG): Multiple stoichiometries and determination of tight binding with a wide spectrum of site affinities. Biochemistry 1990;29:9029-9039.
38. Chen AY, Chiang Y, Gatto B, Liu LF. DNA minor groove-binding ligands: A different class of mammalian DNA topoisomerase I inhibitors. Proc Natl Acad Sci USA 1993;90:8131-8135.
39. Soderlind KJ, Gorodetsky B, Singh AK, Bachur NR, Miller GG, Lown JW. Bis-benzimidazole anticancer agents: Targeting human tumour helicases. Anti-Cancer Drug Design 1999;14:19-36.
40. Lammler G, Herzog H, Saupe E, Schutze HR. Chemoterapeutic studies of Litomosodoides carini infection of Mastomys nataleusis 1. The filaricidal action of 2,6-bis-benzimidazoles. WHO Bull 1971;44:751-756.
41. Kraut E, Fleming T, Segal M, Neidhart J, Beherens BC, Mac Donald J. Phase II study of Pibenzimol in pancreatic cancer - A southwest oncology group study. Invest New Drugs 1999;9:95-96.
42. Ebrahimi SES, Bibby MC, Fox KR, Douglas KT. Synthesis, DNA binding, footprinting and in vitro antitumor studies of a meta-hydroxy analogue of Hoescht 33258. Anti-Cancer Drug Design 1995;10:463-479.
43. Bathini Y, Rao KE, Shea RG, Lown JW. Molecular recognition between ligands and nucleic acids: Novel pyridine and benzoxazole containing agents related to Hoechst 33258 that exhibit altered DNA sequence specificity deduced from footprinting analysis and spectroscopic studies Chem Res Toxicol 1990;3:268-280.
44. Singh MP, Joseph T, Kumar S, Bathini Y, Lown JW. Synthesis and sequence-specific DNA binding of a topoisomerase inhibitory analog of Hoeshst 33258 designed for altered base and sequence recognition. Chem Res Toxicol 1992;5:597-607.
45. Gupta R, Huang L, Wang H, Lown JW. DNA alkylation by minor groove-binding N1-alkoxyalkyl-bisbenzimidazoles. Anti-Cancer Drug Design 1995;10:451-461.
46. Chen AY, Yu C, Bodley A, Peng LF, Liu LF. A new mammalian DNA topoisomerase I poison Hoechst 33342: Cytotoxicity and drug resistance in human cell cultures. Cancer Res 1993;53:1332-1337.
47. Satz AL, White CM, Beerman TA, Bruice TC. Double-stranded DNA binding characteristics and subcellular distribution of a minor groove binding diphenyl ether bisbenzimidazole. Biochemistry 2001; 40:6465-6474.
48. Finlay GJ, Baguley BC. Potentiation by phenylbisbenzimidazoles of cytotoxicity of anticancer drugs directed against topoisomerase II. Eur J Cancer 1990;26:586-589.
49. Singh AK, Lown JW. Design, synthesis and antitumor cytotoxicity of novel bis-benzimidazoles. Anti-Cancer Drug Design 2000;15:265-275.
50. Gupta R, Wang H, Huang L, Lown JW. Design, synthesis, DNA sequence preferential alkylation and biological evaluation of N-mustard derivatives of Hoechst 33258. Anti-Cancer Drug Design 1995;10: 25-41.
51. Mann J, Baron A, Opoku-Boahen Y, Johansson E, Parkinson G, Kelland LR, Neidle S. A new class of symmetric bisbenzimidazole-based DNA minor groove-binding agents showing antitumor activity. J Med Chem 2001;44:138-144.
52. Rinehart KL. Antitumor compounds from tunicates. Med Res Rev 2000;20:1-27.
53. Valoti G, Nicoletti MI, Pellegrino A, Jimeno J, Hendriks H, D'Incalci M, Faircloth G, Giavazzi R. Ecteinascidin 743, a new marine natural product with potent antitumor activity on human ovarian carcinoma xenografts. Clin Cancer Res 1998;4:1977-1983.
54. Erba E, Bergamaschi D, Bassano L, Gamia D, Ronzoni S, Faircloth GT, D'Incalci M. Ecteinascidin-743 (ET-743), a natural marine compound with a unique mechanism of action. Eur J Cancer 2001;37:97-105.
55. Yovine A, Riofrio M, Brain E, Blay JY, Kahatt C, Delaloge S, Bautier L, Coffu P, Jimeno J, Cvitkovic E, Misset JL. Ecteinascidin (ET-743) given as a 24 hour (H) intravenous continuous infusion (IVCI) every 3 weeks: Results of a Phase II trial in patients (pts) with pretreated soft tissue sarcomas (PSTS). Proc Am Soc Clin Oncol 2001;20:36A.
56. Zelek L, Yovine A, Brain E. Ecteinascidin-743 (ET-743) in taxane (T)/anthracycline (A) pretreated advanced/metastatic breast cancer (A/MBC) patients (pts): Preliminary results with the 24 hour (h) continuous infusion (CI) q3 week schedule [Abstract]. 36th Proc Am Soc Clin Oncol 2000 May 20; New Orleans, 19:149a.
57. Foote-Zewail M, Hurley LH. Differenfial rates of reversibility of Ecteinascidin 743-DNA covalent adducts from different sequences lead to migration to favored bonding sites. J Am Chem Soc 2001;123:6485-6495.
58. Pommier Y, Kohlhagen G, Bailly C, Waring M, Mazumder A, Kohn KW. Sequence and structure-selective alkylation of guanine N2 in the DNA minor groove by Ecteinascidin 743, a potent antitumor compound from the Caribbean Tunicate Ecteinascidia turbinata. Biochemistry 1996;35:13303-13309.
59. Seaman FC, Hurley LH. Molecular basis for the DNA sequence selectivity of Ecteinascidin 736 and 743: Evidence for the dominant role of direct readout via hydrogenation bonding. J Am Chem Soc 1998;120:13028-13041.
60. Scotto KW. ET-743; more than an innovative mechanism of action. Anti-Cancer Drugs 2002;13:S3-S6.
61. Takebayashi Y, Pourquier P, Yoshida A, Kohlhagen G, Pommier Y. Poisoning of human DNA topoisomerase I by Ecteinascidin 743, an anticancer drug that selectively alkylates DNA in the minor groove. Proc Natl Acad Sci USA 1999;96:7196-7201.
62. Garcia-Nieto R, Manzanares I, Cuevas C, Gago F. Increased DNA binding specificity for antitumor Ecteinascidin 743 through protein-DNA interactions? J Med Chem 2000;43:4367-4369.
63. 1, activation. Proc Natl Acad Sci USA 2000;97:6775-6779.
64. Cvetkovic RS, Figgitt DP, Plosker GL. ET-743. Drugs 2002;8:1185-1192.
65. Hanka LJ, Dietz A, Gerpheide SA, Kuentzel SL, Martin DG. CC-1065 (NSC-298223) a new antitumor antibiotic. Production, in vitro biological activity, microbiological assays and taxonomy of the producing microrganism. J Antibiot 1978;31:1211-1217.
66. Martin DG, Biles C, Gerpheide SA, Hanka LJ, Krueger WC, McGovern JP, Mizsak A, Neil GL, Stewart JC, Visser J. CC-1065 (NSC-298223) a potent new antitumor agent improved production and isolation, characterization and antitumor activity. J Antibiot 1981;34:1119-1125.
67. Takahashi I, Takahashi K, Ichimura M, Morimoto M, Asano K, Kawamoto I, Tomita F, Nakano H. Duocarmycin A, a new antibiotic from streptomyces. J Antibiot 1988;41:1915-1917.
68. Ichimura M, Ogawa T, Katsumata S, Takahashi K, Takahashi I, Nakano H. Duocarmycins, new antitumor antibiotics produced by streptomyces: Producing organisms and improved production. J Antibiot 1991;44: 1045-1053.
69. Boger DL. The duocarmycins: Synthetic and mechanistic studies. Acc Chem Res 1995;28:20-29.
70. Warpehoski MA, McGovern JP, Mitchell MA, Hurley LH. Molecular basis for sequence-specific DNA alkylation by CC-1065. In: Pullman B, Jortner J, editors. Molecular basis of specificity in nucleic acid-drug interactions. Dordrecht: Kluwer. 1990. pp 531-550.
71. Aristoff PA. CC-1065 analogs: Sequence specific DNA-alkylating agents. Adv MedChem 1993;2:67-110.
72. Boger DL. Design, synthesis and evaluation of functional analogs of CC-t065. In: Bergman J, van der Plas HC, Simonyl M. editors. Heterocycles in bioorganic chemistry. Cambridge: Royal Society of Chemistry. 1991. pp 103-129.
73. Denny WA. DNA minor groove alkylating agents. Curr Med Chem 2001;8:533-544.
74. Reddy BSP, Sharma SK, Lown JW. Recent developments in sequence selective minor groove DNA effectors. Curr Med Chem 2001;8:475-508.
75. Boger DL, Johson DS, Yun W.(+)- and ent-(-)-duocarmycin SA and (+)- and ent-(-)-N-Boc-DSA DNA alkylation properties. Alkylation site models that accommodate the offset AT-rich adenine N3 alkylation selectivity of enantiomeric agents. J Am Chem Soc 1994;116:1635-1656.
76. Boger DL, Ishizaki T, Zarrinmayeh H. Isolation and characterization of duocarmycin-adenine DNA adduct. J Am Chem Soc 1991;113:6645-6649.
77. Hurley LH, Reynolds VL, Swenson GL, Petzold GL, Scahill TA. Reaction of the antitumor antibiotic CC-1065 with DNA: Structure of DNA adduct with DNA sequence specificity. Science 1984;226:843-844.
78. Hurley LH, Lee C-S, McGovern JP, Warpehoski MA, Mitchell MA, Kelly RC, Aristoff PA. Molecular basis for sequence-specific DNA alkylation by CC-1065. Biochemistry 1988;27:3886-3892.
79. Warpehoski MA, Harper DE, Mitchell MA, Monroe TJ. Reversibility of the covalent reaction of CC-1065 and analogues with DNA. Biochemistry 1992;31:2502-2508.
80. McGovern JP, Clarke GL, Pratt EA, DeKoning TF. Preliminary toxicity studies with the DNA-binding antibiotic CC-1065. J Antibiot 1984;37:63-70.
81. Boger DL, Boyce CW, Garbaccio RM, Goldberg J. CC-1065 and the duocarmycins: Synthetic studies. Chem Rev 1997;97:787-828.
82. Boger DL, McKie JA, Cai H, Cacciari B, Baraldi PG. Synthesis and properties of substituted CBI analogs of CC-1065 and the duocarmycins incorporating the 7-methoxy-1,2,9,9a-tetrahydrocyclopropa[c] benz[e]indol-4-one (MCBI) alkylatioh subunit: Magnitude of electronic effects on the functional reactivity. J Org Chem 1996;61:1710-1729.
83. Boger DL, Yun W. Role of the CC-1065 and duocarmycin N2 substituent: Validation of a direct relationship between solvolysis, chemical stability and in vitro biological potency. J Am Chem Soc 1994;116:5523-5524.
84. Boger DL, Jenkins TJ. Synthesis, X-ray structure and properties of fluorocyclopropane analogs of the duocarmycins incorporating the 9,9-difluoro-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (F2CBI) alkylation subunit. J Am Chem Soc 1996;118:8860-8870.
85. Boger DL, Turnbull P. Synthesis and evaluation of CC-1065 and duocarmycin analogs incorporating the A-hexahydrocyclopropa[c]naphtho[2,1-b]azepin-6-one (CNA) alkylation subunit-structural features that govern reactivity and reaction regioselectivity. J Org Chem 1997;62:5849-5863.
86. Boger DL, Hughes TV, Hedrick MP. Synthesis, chemical properties, and biological evaluation of CC-1065 and duocarmycin analogues incorporating the 5-methoxycarbonyl-1,2,9,9a-tetrahydrocyclopropa[c] benz[e]indol-4-one alkylation subunit. J Org Chem 2001;66:2207-2216.
87. Mohamadi F, Spees MM, Staten GS, Marder P, Kipka JK, Johnson DA, Boger DL, Zarrinmayeh H. Total synthesis and biological properties of novel antineoplastic (chloromethyl)furanoindolines: An asymmetric hydroboration mediated synthesis of the alkylation subunit. J Med Chem 1994;37:232-239.
88. Muratake H, Okabe K, Takahashi M, Tonegawa M, Natsume M. Synthesis of furan and thiophene analogs of duocarmycin SA. Chem Pharm Bull 1997;45:799-806.
89. Muratake H, Hayakawa A, Natsume M. Preparation of benzene, furan and thiophene analogs of duacarmycin SA employing a newly-devised phenol-forming reaction. Chem Pharm Bull 2000;48:1558-1566.
90. Patel VF, Andis SL, Enkema JK, Johnson DA, Kennedy JH, Mohamadi F, Schultz RM, Soose DJ, Spees MM. Total synthesis of seco (+)- and ent-(-)-oxaduocarmycin SA: Construction of the (chloromethyl)indoline alkylating subunit by a novel intramolecular ary radical cyclization onto a vinyl chloride. J Org Chem 1997;62:8868-8874.
91. Howard TH, Lingerfelt BM, Purnell BL, Scott AE, Price CA, Townes HM, Mc Nulty L, Handl HL, Summerville K, Hudson SJ, Bowen JP, Kiakos K, Hartley JA, Lee M. Novel furano analogues of duocarmycin C1 and C2: Design, synthesis and biological evaluation of seco-iso-cyclopropylfurano[2,3-e]indoline (seco-iso-CFI) and seco-cyclopropyltetrahydrofurano[2,3-f]quinoline (seco-CFQ) analogues. Bioorg Med Chem 2002;10:2941-2952.
92. Enjo J, Castedo L, Tojo G. Photochemistry of tosylstilbenoids in the preparation of complex heterocyclic compounds. Synthesis of a cyclopropafuroindolone analogue of the DNA-alkylating section of the anti-tumor compound CC-1065. Org Lett 2001;3:1343-1345.
93. Boger DL, Boyce CW. Selective metal cation activation of a DNA alkylating agent: Synthesis and evaluation of methyl 1,2,9,9a-tetrahydrocyclopropa[c] pyrido[3,2-e]indol-4-one-7-carboxylate (CpyI). J Org Chem 2000;65:4088-4100.
94. Boger DL, Santillan A, Searcey M, Brunette SR, Wolkenberg SE, Hedrick MP, Jin Q. Synthesis and evaluation of 1,2,8,8a-tetrahydrocyclopropa[c]pyrrolo[3,2- e]indol-4(5H)-one, the parent alkylation subunit of CC-1065 and the duocarmycins: Impact of the alkylation subunit substituents and its implications for DNA alkylation catalysis. J Org Chem 2000;65:4101-4111.
95. Bryson TA, Roth GA. Cyclopropane chemistry related to the alkaloid CC-1065. Tetrahedron Lett 1988; 29:2167-2170.
96. Baraldi PG, Cacciari B, Pineda de Las Infantas MJ, Romagnoli R, Spalluto G, Cozzi P, Mongelli N. Synthesis, chemical solvolytic stability and preliminary biologica evaluation of (±)N-Boc-CPzI: A pyrazole analog of the left-hand segment of the antitumor agent CC-1065. Anti-Cancer Drug Design 1997;12:67-74.
97. Baraldi PG, Cacciari B, Romagnoli R, Spalluto G, Boyce CW, Boger DL. Resolution of a CPzI precursor, synthesis and biological evaluation of (+) and (-)-N-Boc-CPzI: A further validation of the relationship between chemical solvolytic stability and cytotoxicity. Bioorg Med Chem Lett 1999;9:3087-3092.
98. Baraldi PG, Cacciari B, Romagnoli R, Spalluto G, Gambari R, Bianchi N, Passadore M, Ambrosino P, Mongelli N, Cozzi P, Geroni C. Synthesis, cytotoxicity, antitumor activity and sequence selectivity binding of two pyrazole analogs structurally related to the antitumor agents U-71,184 and Adozelesin. Anti-Cancer Drug Design 1997;12:555-576.
99. Baraldi PG, Cacciari B, Guiotto A, Romagnoli R, Spalluto G, Zaid AN, Capolongo L, Cozzi P, Geroni C, Mongelli N. Synthesis, solvolytic stability and cytotoxicity of a modified derivative of CPzI, a pyrazole analog of the alkylation subunit of the antitumor agent CC-1065: Effect of the nitrogen substitution on the functional reactivity. Il Farmaco 1997;52:717-723.
100. Milbank JBJ, Tercel M, Adwell GJ, Wilson WR, Hogg A, Denny WA. Synthesis of 1-substituted 3-(chloromethyl)-6-aminoindoline (6-amino-seco-CI) minor groove alkylating agents and structure activity relationships for the cytotoxicity. J Med Chem 1999;42:649-668.
101. 3H-benz[e]indole (amino-seco-CBI-TMI) and related 5-alkylamino analogues. New DNA minor groove alkylating agents. J Org Chem 1998;63:9414-9420.
102. Tercel M, Gieseg MA, Denny WA, Wilson WR. Synthesis and cytotoxicity of amino-seco-DSA: An amino analogue of the DNA alkylating agent duocarmycin SA. J Org Chem 1999;64:5946-5953.
103. Coté S, Momparler RL. Evaluation of the antineoplastic activity of adozelesin alone and in combination with 5-aza-2′-deoxycytidine and cytosine arabinoside on DLD-1 human colon carcinoma cells. Anti Cancer Drugs 1993;4:327-333.
104. Li LH, Kelly RC, Warpehoski MA, McGovern JP, Gebhard I, Dekoning TF. Adozelesin, a selected lead among cyclopropylpyrroloindole analogs of the DNA binding antibiotic CC-1065. Inv New Drugs 1991; 9:137-148.
105. Li LH, DeKoning TF, Kelly RC, Krueger WC, McGovern JP, Padbury GE, Petzold GL, Wallace TL, Ouding RJ, Prairie MD, Gebhard I. Cytoxicity and antitumor activity of carzelesin, a prodrug cyclopropylpyrroloindole analogue. Cancer Res 1992;52:4904-4913.
106. Mitchell MA, Kelly RC, Wicnieski NA, Hatzenbuhler NT, Williams MG, Petzold GL, Slightom JL, Siemieniak DR. Synthesis and DNA cross-linking by a rigid CPI dimer. J Am Chem Soc 1991;113:8994-8995.
107. Pitot HC, Reid JM, Sloan JA, Ames MM, Adjei AA, Robin J, Bagniewski PG, Atherton P, Rayson D, Goldberg RM, Erlichman CA. Phase I study of bizelesin (NSC 615291) in patients with advanced solid tumors. Clin Cancer Res 2002;8:712-717.
108. Volpe DA, Tomaszewski JE, Parchment RE, Garg A, Flora KP, Murphy MJ, Grieshaber CK. Myelotoxic effects of the bifunctional alkylating agent bizelesin on human, canine and murine myeloid progenitor cells. Cancer Chemother Pharmacol 1996;39:143-149.
109. Kobayashi E, Okamoto A, Asada M, Okabe M, Nagamura S, Asai A, Saito A, Gomi K, Hirata T. Characteristics of antitumor activity of KW-2189, a novel water-soluble derivative of duocarmycin, against murine and human tumors. Cancer Res 1994;54:2404-2410.
110. Kobayashi E, Okamoto A, Asada M, Okabe M, Nagamura S, Asai A, Saito H, Gomi K, Hirata T. Characteristics of antitumor activity of KW-2189, a novel water-soluble derivative of duocarmycin, against murine and human tumors. Cancer Res 1994;54:2404-2410.
111. Amishiro N, Nagamura S, Murakata C, Okamoto A, Kobayashi E, Asada M, Gomi K, Tamaoky T, Okabe M, Yamaguchi N, Yamaguchi K, Saio H. Synthesis and antitumor activity of duocarmycin derivatives: Modification at C-8 position of A-ring pyrrole compounds bearing the simplified DNA-binding groups. Bioorg Med Chem 2000;8:381-391.
112. Nagamura S, Asai A, Amishiro N, Kobayashi E, Gomi K, Saito H. Synthesis and antitumor activity of duocarmycin derivatives: A-ring pyrrole compounds bearing cinnamoyl groups. J Med Chem 1997;40: 972-979.
113. Amishiro N, Nagamura S, Kobayashi E, Gomi K, Saito H. New water-soluble duocarmycin derivatives: Synthesis and antitumor activity of A-ring pyrrole compounds bearing beta-heteroarylacryloyl groups. J Med Chem 1999;42:669-676.
114. Fukuda Y, Furuta H, Kusama Y, Ebisu H, Oomori Y, Terashima S. Cyclopropapyrroloindole derivative (AT-3510) bearing methoxycarbonyl and trifluoromethyl groups. J Med Chem 1999;42:1448-1458.
115. Fakuda Y, Furuta H, Kusuma Y, Ebisu H, Oomori Y, Terashima S. The novel cyclopropapyrroloindole (CPI) bisalkylators bearing methoxycarbonyl and trifluoromethyl groups. Bioorg Med Chem Lett 1998;8:1387-1390.
116. Fukuda Y, Seto S, Furuta H, Ebisu H, Oomori Y, Terashima S. The novel cyclopropapyrroloindole (CPI) bisalkylators bearing 3,3′-(1,4-phenylene) diacryloyl group as a linker. Bioorg Med Chem Lett 1998;8: 2003-2004.
117. Fukuda Y, Seto S, Furuta H, Ebisu H, Oomori Y, Terashima S. Novel seco cyclopropa[c]pyrrolo[3,2-e]indole bisalkylators bearing a 3,3′- arylenebisacryloyl group as a linker. J Med Chem 2001;44:1396-1406.
118. Boger DL, Johnson DS. CC-1065 and the duocarmycins: Understanding their biological function through mechanistic studies. Angew Chem Intl Ed Engl 1996;35:1438-1474.
119. Wang Y, Yuan H, Ye W, Wright SC, Wang H, Larrick JW. Synthesis and preliminary biological evaluations of CC-1065 analogues: Effects of different linkers and terminal amides on biological activity. J Med Chem 2000;43:1541-1549.
120. Thurston DE. Advances in the study of pyrrolo [2,1-c] [1,4]-benzodiazepine (PBD) antitumor antibiotics. In: Neidle S, Waring MJ, editors. Molecular aspects of anticancer drug-DNA interactions. London: The Macmillan Press Ltd., 1993. pp 54-88.
121. Hurley LH, Reck T, Thurston DE, Langley DR, Holden KG, Hertzberg RP, Hoover JRE, Gallagher G, Faucette LF, Mong SM, Johnson RK. Pyrrolo [1,4] benzodiazepine antitumor antibiotics: Relationship of DNA alkylation and sequenze specificity to the biological activity of natural and synthetic compounds. Chem Res Toxicol 1988;1:258-268.
122. Hurley LH. Pyrrolo [1,4] benzodiazepine antitumor antibiotics. Comparative aspects of anthramycin, tomamymaycin and sibiromycin. J Antibiot 1977;30:349-370.
123. Hurley LH. Petrusek R. Proposed structure of the anthramycin-DNA adduct. Nature 1979;282:529-531.
124. Kopka ML, Goodsell DS, Baikalov I, Grzeskowiak K, Cascio D, Dickerson RE. Crystal structure of a covalent DNA-drug adduct: Anthramycin bound to C-C-A-A-C-G-T-T-G-G and a molecular explanation of specificity. Biochemistry 1994;33:13593-13610.
125. Boyd FL, Stewart D, Remers WA, Barkley MD, Hurley LH. Characterization a unique tomaymycin d(CICGAATTCICG)2 adduct containing two drug molecules per duplex by NMR fluorescence and molecular modeling studies. Biochemistry 1990;29:2387-2403.
126. Petrusek RL, Anderson GL, Garner TF, Quinton FL, Fannin L, Kaplan DJ, Zimmer SG, Hurley LH. Pyrrolo [1,4] benzodiazepine antibiotics. Proposed structures and characteristics of the in vitro deoxyribonucleic acid adducts of anthramycin, tomaymycin, sibiromycin and neothramycins. Biochemistry 1981;20:1111-1119.
127. Petrusek RL, Uhlenhopp EL, Duteau N, Hurley LH. Reaction of anthramycin with DNA. Biological consequences of DNA damage in normal and xerederma pigmento sum cell. J Biol Chem 1982;257:6207-6216.
128. Hurley LH, Gairola C, Zmijewski M. Pyrrolo [1,4] benzodiazepine antitumor antibiotics. In vitro interaction of anthramycin, tomaymycin and sibiromycin with DNA using specifically radiolabelled molecules. Biochim Biophys Acta 1977;475:521-535.
129. Arima K, Kohsaka M, Tamura G, Imanaka H, Sakai U. Tomaymycin, a new antibiotic. I. Isolation and properties of tomaymycin. J Antibiot 1972;25:437-444.
130. Takeuchi T, Miyamoto M, Ishizuka M, Naganawa H, Kondo S, Hamada M, Umezawa H. Neothramycins A and B, new antitumor antibiotics. J Antibiot 1976;29:93-96.
131. Grunberg E, Prince HN, Titsworth E, Beskid G, Tendler MD. Chemotherapeutic properties of anthramycin. Chemotherapy 1966;11:249-260.
132. Remers WA. The chemistry of antitumor antibiotics. New York, NY: Wiley, 1988. 2:28-92.
133. Horwitz SB, Chang SC, Grollman AP, Borkovec AB. Chemosterilant action of anthramycin: A proposed mechanism. Science 1971;147:159-161.
134. Mosman T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Met 1983;65:55-63.
135. Korman S, Tendler MD. Clinical investigation of cancer chemoterapeutic agents for neoplastic disease. J New Drugs 1965;5:275-285.
136. Zbinden G. Drug toxicity and its impact on drug evaluation in man. In: Plattner, chemotherapy of cancer. Proceedings of International Symposium Lugano. Amsterdam/London/New York: Elsevier, 1964, pp 303-310.
137. Cargill C, Bachmann E, Zbinden G. Effects of daunomycin and anthramycin on electrocardiogram and mitochondrial metabolism of the rat hearth. J Natl Cancer Inst 1974;53:481-486.
138. Goodman J, Hochstein P. Generation of free radicals and lipid peroxidation by redox cycling of adriamycin and daunomycin. Biochem Biophys Res Commun 1977;77:797-803.
139. Lubawy WC, Dallam RA, Hurley LH. Protection against anthramycin-induced toxicity in mice by coenzyme Q10. J Natl Cancer Inst 1980;64:105-109.
140. Lubawy WC, Whaley J, Hurley LH. Coenzyme Q 10 or alpha-tocopherol reduce the acute toxicity of anthramycin in mice. Res Commun Chem Pathol Pharmacol 1979;24:401-404.
141. Langlois N, Rojas-Rousseau A, Gaspard C, Werner GH, Darro F, Kiss R. Synthesis and cytotoxicity on sensitive and doxorubicin-resistant cell lines of new pyrrolo [2,1-c] [1,4]-benzodiazepines related to anthramycin. J Med Chem 2001;44:3754-3757.
142. Baraldi PG, Leoni A, Cacciari B, Manfredini S, Simoni D. Synthesis and antitumor activity of a new class of pyrazolo[4,3-e]pyrrolo[1,2-a][1,4] diazepinone analogs of pyrrolo[1,4]benzodiazepines (PBDs). Bioorg Med Chem Lett 1993;3:2511-2514.
143. Baraldi PG, Leoni A, Cacciari B, Manfredini S, Simoni D, Bergomi M, Menta E, Spinelli S. Synthesis and antitumor activity of a new class of pyrazolo[4,3-e]pyrrolo[1,2-a][1,4]diazepinone analogs of pyrrolo[1,4] benzodiazepines. J Med Chem 1994;37:4329-4337.
144. Thurston DE, Bose DS. Synthesis and DNA interactive pyrrolo [2,1-c] [1,4]-benzodiazepines. Chem Rev 1994;94:433-465.
145. Langley DR, Thurston DE. A versatile and efficient synthesis of carbinolamine-containing pyrrolo[1,4]-benzodiazepines via the cyclization of N-(2-aminobenzoyl)pyrrolidine-2-carboxaldehyde diethyl thioacetals: Total synthesis of prothracarcin. J Org Chem 1987;52:91-97.
146. Thurston DE, Bose DS, Howard PW, Jenkins TC, Leoni A, Baraldi PG, Guiotto A, Cacciari B, Kelland LR, Faloppe MP, Rault S. Effect of A-ring modifications on the DNA-binding behavior and cytotoxicity of pyrrolo [2,1-c] [1,4]-benzodiazepines. J Med Chem 1999;42:1951-1964.
147. Baraldi PG, Cacciari B, Guiotto A, Romagnoli R, Spalluto G. Heterocyclic analogs of pyrrolo [2,1-c] [1,4]-benzodiazepines. Synthesis and structural requirements for their biological activity. Recent Res Dev In Org Chem 1998;2:567-591.
148. Farmer JD, Gustafson GR, Conti A, Zimmt MB, Suggs JW. DNA binding properties of a new class of linked anthramycin analogs. Nucleic Acid Res 1991;19:899-903.
149. Bose DS, Thompson AS, Ching JS, Hartley JA, Berardini MD, Jenkins TC, Neidle S, Hurley LH, Thurston DE. Rational design of a highly efficient irreversible DNA interstrand cross-linking agent based on the pyrrolobenzodiazepine ring system. J Am Chem Soc 1992;114:4939-4941.
150. Bose DS, Thompson AS, Smellie M, Berardini MD, Hartley JA, Jenkins TC, Neidle S, Thurston DE. Effect of linker length on DNA-binding affinity, cross-linking efficiency and cytotoxicity of C8-linked pyrrolobenzodiazepine dimers. Chem Comm 1992;20:1518-1520.
151. Thurston DE, Bose DS, Thompson AS, Howard PW, Leoni A, Croker SJ, Jenkins TC, Neidle S, Hartley JA, Hurley LH. Synthesis of sequence-selective C8-linked of pyrrolo [2,1-c] [1,4]-benzodiazepine DNA interstrand cross-linking agents. J Org Chem 1996;61:8141-8147.
152. Smellie M, Kelland LR, Thurston DE, Souhami RL, Hartley JA. Cellular pharmacology of novel C8-linked anthramycin-based sequence-selective DNA minor-groove crosslinking agents. Br J Cancer 1994;70:48-53.
153. Jenkins TC, Hurley LH, Neidle S, Thurston DE. Structure of a covalent DNA minor-groove adduct with a pyrrolobenzodiazepine dimer. Evidence for sequence-specific interstrand cross-linking. J Med Chem 1994;37:4529-4537.
154. Walton MI, Goddard P, Kelland LR, Thurston DE, Harrap KR. Preclinical pharmacology and antitumor activity of the novel sequence-selective DNA minor-groove cross-linking agent DSB-120. Cancer Chemother Pharmacol 1996;38:431-438.
155. Morris SJ, Thurston DE, Nevell TG. Evaluation of the electrophilicity of DNA-binding pyrrolo [2,1-c] [1,4]-benzodiazepines by HPLC. J Antibiot 1990;43:1286-1292.
156. Kamal A, Laxman E, Reddy PSMM. Reductive cyclization of ω-azido/nitrocarbonyl compounds by samarium iodide: A facile preparation of DNA-binding pyrrolo [2,1-c] [1,4]-benzodiazepine and its dimer. Tethrahedron Lett 2000;41:8631-8634.
157. Kamal A, Laxman E, Laxman N, Rao NV. Synthesis of pyrrolo [2,1-c] [1,4]-benzodiazepines via reductive cyclization of ω-azido carbonyl compounds by TMSI: An efficient preparation of antibiotic DC-81 and its dimers. Bioorg Med Chem Lett 2000;10:2311-2313.
158. Gregson SJ, Howard PW, Hartley JA, Brooks NA, Adams LJ, Jenkins TC, Kelland LR, Thurston DE. Design, synthesis and evaluation of a novel pyrrolobenzodiazepine DNA-interactive agent with highly efficient cross-linking ability and potent cytotoxicity. J Med Chem 2001;44:737-748.
159. Reddy BSP, Damayanthi Y, Reddy Narayan BS, Lown JW. Design, synthesis and in vitro cytotoxicity studies of novel pyrrolo [2,1-c] [1,4] benzodiazepine (PBD)-polyamide conjugates and 2,2′-PBD dimers. Anti-Cancer Drug Design 2000;15:225-238.
160. Kamal A, Laxman N, Ramesh G, Neelima K, Kondapi AK. Synthesis of novel non-cross-linking pyrrolobenzodiazepines with remarkable DNA affinity and potent antitumor activity. Chem Comm 2001;5:437-438.
161. Kamal A, Ramesh G, Laxman N, Ramulu P, Srinivas O, Neelima K, Kondapi AK, Sreenu VB, Nagarajaram HA. Design, synthesis and evaluation of new noncross-linking pyrrolobenzodiazepine dimers with efficient DNA binding ability and potent antitumor activity. J Med Chem 2002;45:4679-4688.
162. For reviews specifically focused on distamycin A see: (a) Cozzi P, Mongelli N. Cytotoxics derived from distamycin and congeners. Curr Pharm Design 1998;4:181-201;
163. (b) Bailly C, Chaires JB. Sequence-specific DNA minor groove binders. Design and synthesis of netropsin and distamycin analogues. Bioconjugate Chem 1998;9:513-538;
164. (c) Baraldi PG, Cacciari B, Spalluto G, Romagnoli R. DNA minor groove alkylating agents sructurally related to distamycin A. Expert Opin Ther Pat 2000;6:891-904;
165. (d) Marchini S, Broggini M, Sessa C, D'Incalci M. Development of distamycin-related DNA binding anticancer drugs. Expert Opin Invest Drugs 2001;10:1703-1714.
166. Arcamone F, Penco S, Orezzi PG, Nicolella V, Pirelli A. Structure and synthesis of distamycin A. Nature 1964;203:1064-1065.
167. Grehn L, Ragnarsson U. Novel efficient total synthesis of antiviral antibiotic distamycin A. J Org Chem 1981;46:3492-3497.
168. Baird EE, Dervan PB. Solid phase synthesis of polyamides containing imidazole and pyrrole amino acids. J Am Chem Soc 1996;118:6141-6146.
169. Lee S, Inselburg J. In vitro sensitivity of Plasmodium falciparum to drugs that bind DNA or inhibit its synthesis. J Parasitol 1993;79:780-782.
170. 2 determined by two-dimensional NMR. J Am Chem Soc 1990;112:1393-1399.
171. Woods CR, Faucher N, Eeschgfaller B, Bair KW, Boger D. Synthesis and DNA binding properties of saturated distamycin analogues. Bioorg Med Chem Lett 2002;12:2647-2650.
172. Bhattacharya S, Thomas M. DNA binding properties of novel distamycin analogs that lack the leading amide unit at the N-terminus. Biochem Biophys Res Comm 2000;267:139-144.
173. Bhattacharya S, Thomas M. Facile synthesis of oligopeptide distamycin analogs devoid of hydrogen bond donors or acceptors at the N-terminus: Sequence-specific duplex DNA binding as a function of peptide chain length. Tetrahedron Lett 2000;41:5571-5575.
174. Zaffaroni N, Lualdi S, Villa R, Bellarosa D, Cermele C, Felicetti P, Rossi C, Orlandi L, Daidone MG. Inhibition of telomerase activity by a distamycin derivative: Effects on cell proliferation and induction of apoptosis in human cancer cells. Eur J Cancer 2002;38:1792-1801.
175. Wang W, Lown JW. Anti-HIV-1 activity of linked lexitropsins. J Med Chem 1992;35:2890-2897.
176. Neamati N, Mazumder A, Sunder S, Owen JM, Tandon M, Lown JW, Pommier Y. Highly potent synthetic polyamides, bisdistamycins and lexitropsins as inhibitors of human immunodeficiency virus type 1 integrase. Mol Pharm 1998;54:280-290.
177. Dyatkina NB, Roberts CD, Keicher JD, Dai Y, Nadherny JP, Zhang W, Schmitz U, Kongpachith A, Fung K, Novikov AA, Lou L, Velligan M, Khorlin AA, Chen MS. Minor groove DNA binders as antimicrobial agents. 1. Pyrrole tetramides are potent antibacterial against Vancomycin resistant Enterococci and Methicillin resistant Staphylococcus aureus. J Med Chem 2002;45:805-817.
178. Howard OMZ, Oppenheim JJ, Hollingshead MG, Covey JM, Bigelow J, Mc Cormack JJ, Buckheit RW, Clanton DJ, Turpin JA, Rice WG. Inhibition of in vitro and in vivo HIV replication by a dystamycin analogue that interferes with chemochine receptor function: a candidate for chemotherapeutic and microbicidal application. J Med Chem 1998;41:2184-2193.
179. Burli RW, Ge Y, White S, Baird EE, Touami SM, Taylor M, Kaizerman JA, Moser HE. DNA binding ligands with excellent antibiotic potency against drug-resistant gram-positive bacteria. Bioorg Med Chem Lett 2002;12:2591-2594.
180. Ryabinin VA, Zakharova OD, Yurchenko EY, Timofeeva OA, Martyanov IV, Tokarev AA, Belanov EF, Bormotov NI, Tarrago-Litvak L, Andreola ML, Litvak S, Nevinsky GA, Sinyakov AN. Synthesis and evaluation of oligo-1,3- thiazolecarboxamide derivatives as HIV-1 reverse transcriptase inhibitors. Bioorg Med Chem 2000;8:985-993.
181. Arcamone FM, Animati F, Barbieri B, Configliacchi E, D'Alessio R, Geroni C, Giuliani FC, Lazzari E, Menozzi M, Mongelli N, Penco S, Verini MA. Synthesis, DNA-binding properties, and antitumor activity of novel distamycin derivatives. J Med Chem 1989;32:774-778.
182. D'Alessio R, Geroni C, Biasioli G, Pesenti E, Grandi M, Mongelli N. Structure-activity relationship of novel distamycin A derivatives: Synthesis and antitumor activity. Bioorg Med Chem Lett 1994;4:1467-1472.
183. Pezzoni G, Grandi M, Biasioli G, Capolongo L, Ballinari D, Giuliani FC, Barbieri B, Pastori A, Pesenti E, Mongelli N, Spreafico F. Biological profile of FCE 24517, a novel benzoyl mustard analog of distyamycin A. Br J Cancer 1991;64:1047-1050.
184. Marchini S, Cirò M, Gallinari F, Geroni C, Cozzi P, D'Incalci M, Broggini M. α-Bromoacriloil derivative of distamycin A (PNU 151807): A new non covalent minor groove binder with antineoplastic activity. Br J Cancer 1999;80:991-997.
185. Cozzi P, Beria I, Caldarelli M, Capolongo L, Geroni C, Mongelli N. Cytotoxic halogenoacrylic derivatives of distamycin A. Bioorg Med Chem Lett 2000;10:1269-1272.
186. Cozzi P, Beria I, Caldarelli M, Geroni C, Monelli N, Pannella G. Cyotoxic α-bromoacrylic derivatives of distamycin analogues modified at the amicino moiety. Bioorg Med Chem Lett 2000;10:1273-1276.
187. Geroni C, Pannella G, Capolongo L. Antitumor activity of PNU-166196, a novel DNA minor groove binder selected for clinical development. Proc Am Assoc Cancer Res 2000;41:265.
188. Geroni C, Marchini S, Cozzi P, Galliera E, Ragg E, Colombo T, Battaglia R, Howard M, D'Imcalci M, Broggini M. Brostallicin, a novel anticancer agent whose activity is enhanced upon binding to glutathione. Cancer Res 2002;62:2332-2336.
189. Beria I, Caldarelli M, Geroni C, Monelli N, Reinach B, Vignati L, Cozzi P. Cytotoxic alpha-bromomoacrylic derivatives of low molecular weight. Bioorg Med Chem Lett 2002;12:1467-1471.
190. Pezzoni G, Grandi M, Biasoli G, Capolongo L, Ballinari D, Giuliani FC, Barbieri B, Pastori A, Pesenti E, Mongelli N, Spreafico F. Biological profile of FCE 24517, a novel benzoyl mustard analog of distamycin A. Brit J Cancer 1991;64:1047-1050.
191. Ghielmini M, Bosshard G, Capolongo L, Geroni C, Pesenti E, Torri V, D'Incalci M, Cavalli F, Sessa C. Estimation of the haematological toxicity of minor groove alkylators using tests on human cord blood cells. Brit J Cancer 1997;75:878-883.
192. Viallet J, Stewart D, Shepherd F, Ayoub J, Cormier Y, Di Pietro N, Steward W. Tallimustine is inactive in patients with previously treated small-cell lung cancer - A phase II trial of the National Cancer Institute of Canada clinical trials group. Lung Cancer 1996;15:367-373.
193. Broggini M, Coley HL, Pesenti E, Wyatt MD, Hartley JA, D'Incalci M. DNA sequence-specific adenine alkylation by the novel antitumor drug Tallimustine (FCE 24517), a benzoyl nitrogen mustard derivative of distamycin. Nucleic Acids Res 1995;23:81-87.
194. Bigoni M, Salvatore C, Palma C, Manzini S, Animati F, Lombardi P, Pratesi G, Supino R, Zunino F. Cytotoxic and antitumor activity of MEN 10710, a novel alkylating derivative of distamycin. Anti-Cancer Drugs 1997;8:845-852.
195. Bartulewicz D, Bielawwski K, Bielawska A, Rozanski A. Synthesis, molecular modelling, and antiproliferative and cytotoxic effects of carbocyclic derivatives of distamycin with chlorambucil moiety. Eur J Med Chem 2001;36:461-467.
196. Bardos TJ, Datta-Gupta N, Hebborn P, Triggle DJ: A study of comparative chemical and biological activities of alkylating agents. J Med Chem 1964;8:167-174.
197. Cozzi P, Beria I, Biasoli G, Caldarelli M, Capolongo L, D'Alessio R, Geroni C, Mazzini S, Ragg E, Rossi C, Monelli N. Novel phenyl nitrogen mustard and half-mustard derivatives of distamycin A. Bioorg Med Chem Lett 1997;7:2985-2990.
198. Cozzi P, Beria I, Caldarelli M, Capolongo M, Geroni C, Mazzini S, Ragg E. Phenyl sulfur mustard derivatives of distamycin A. Bioorg Med Chem Lett 2000;10:1653-1656.
199. Cozzi P, Beria I, Biasoli G, Caldarelli M, Capolongo L, Geroni C, Mongelli N. Novel phenyl nitrogen mustard and half-mustard derivatives of amidino-modified distamycin A. Bioorg Med Chem Lett 1997;7:2979-2984.
200. Wyatt MD, Garbiras BJ, Haskell MK, Lee M, Souhami RL, Hatley JA. Structure-activity relationship of a series of nitrogen mustard- and pyrrole-containing minor groove-binding agents related to distamycin. Anti-Cancer Drug Design 1994;9:511-525.
201. Lee M, Simpson JE, Woo S, Kaenzig C, Anlezark GM, Eno-Amooquaye E, Burke PJ. Synthesis of an aminopropyl analog of the experimental anticancer drug tallimustine, and activation of its 4-nitrobenzylcarbamoyl prodrug by nitroreductase and NADH. Bioorg Med Chem Lett 1997;7:1065-1070.
202. Baraldi PG, Cozzi P, Geroni C, Mongelli N, Romagnoli R, Spalluto G. Novel benzoyl nitrogen mustard derivatives of pyrazole analogues of distamycin A: Synthesis and antitumor activity. Bioorg Med Chem 1999;17:251-262.
203. Marchini S, Cozzi P, Beria I, Geroni C, Capolongo L, D'Incalci M, Broggini M. Sequence-specific DNA alkylation of novel tallimustine derivatives. Anti-Cancer Drug Design 1998;13:193-205.
204. Baraldi PG, Beria I, Cacciari B, Capolongo L, Cozzi P, Mongelli N, Romagnoli R, Spalluto G. Structure-activity relationship of novel tallimustine derivatives: Synthesis and antitumor activity. Bioorg Med Chem Lett 1996;6:1247-1252.
205. Lee HH, Boyd M, Gravatt GL, Denny WA. Pyrazole analogues of the bispyrrolecarboxamide anti-tumor antibiotics: Synthesys, DNA binding and anti-tumor properties. Anti-Cancer Drug Design 1991;6:501-517.
206. Baraldi PG, Romagnoli R, Spalluto G, Cozzi P, Mongelli N, Bianchi N, Gambari R. DNA sequence-recognizing properties of minor groove alkylating agents: Effects of the replacement of N-methylpyrrole by an N-methylimidazole on Tallimustine and its own homologous. Arzneim Forsh Drug Res 2000;50:309-315.
207. Lee M, Rhodes AL, Wyatt MD, D'Incalci M, Forrow S, Hartley JA. In vitro cytotoxicity of GC sequence directed alkylating agents related to distamycin. J Med Chem 1993;36:863-870.
208. Hartley JA, Wyatt MD, Garbiras BJ, Richter CBJ, Richter C, Lee M. Probing the importance of the second chloroethyl arm of a benzoic acid mustard derivative of an imidazole-containing analogue of distamycin. Bioorg Med Chem Lett 1994;4:2421-2424.
209. Xie G, Gupta R, Lown JW. Design, synthesis, DNA sequence preferential alkylation and biological evaluation of N-mustard derivatives of distamycin and netropsin analogues. Anti-Cancer Drug Design 1995;10:389-409.
210. Baraldi PG, Beria I, Cacciari B, Capolongo L, Cozzi P, Franzetti C, Monelli N, Romagnoli R, Spalluto G. Synthesis and antitumor activity of novel distamycin derivatives. Biorg Med Chem Lett 1996;6:1241-1246.
211. Baraldi PG, Balboni G, Romagnoli R, Spalluto G, Cozzi P, Geroni C, Mongelli N, Rutigliano C, Bianchi N, Gambari R. PNU 157977: A new potent antitumor agent exhibiting low in vivo toxicity in mice injected with L1210 leukemia cells. Anti-Cancer Drug Design 1999;14:71-76.
212. Baraldi PG, Romagnoli R, Pavani MG, Nuñez MDC, Bingham JP, Hartley JA. Benzoyl and cinnamoyl nitrogen mustard derivatives of tallimustine benzoetherocyclic analogues: Synthesis and antitumor activity. Bioorg Med Chem 2002;10:1611-1618.
213. Baraldi PG, Romagnoli R, Beria I, Cozzi P, Geroni C, Mongelli N, Bianchi N, Mischiati C, Gambari R. Synthesis and antitumor activity of new benzoheterocyclic derivatives of distamycin A. J Med Chem 2000;43:2675-2684.
214. Baraldi PG, Beria I, Cozzi P, Bianchi N, Gambari R, Romagnoli R. Synthesis and growth inhibition activity of α-bromoacrylic heterocyclic and benzoheterocyclic derivatives of distamycin A modified on the amidino moiety. Bioorg Med Chem 2003;11:965-975.
215. Sondhi SM, Praveen BS, Lown JW. Lexitropsin conjugates: Action on DNA targets. Curr Med Chem 1997;4:313-358.
216. Baraldi PG, Romagnoli R, Martinez A, Pineda de las Infantas MJ, Gallo MA, Espinosa A, Rutigliano C, Bianchi N, Gambari R. Design, synthesis and biological activity of 5-fluorouracil-distamycin hybrids. Med Chem Res 2001;10:390-403.
217. Hartley JA, Bingham JP, Souhami RL. DNA sequence selectivity of guanine-N7 alkylation by nitrogen mustards is preserved in intact cells. Nucleic Acids Res 1992;20:3175-3178.
218. Baraldi PG, Romagnoli R, Entrena Guadix A, Pineda de las Infantas MJ, Gallo MA, Espinosa A, Martinez A, Bingham JP, Hartley JA. Design, synthesis and biological activity of hybrid compounds between uramustine and DNA minor groove binder distamycin A. J Med Chem 2002;45:3630-3638.
219. Nicolaou KC, Dai WM. Chemistry and biology of enediyne anticancer antibiotics. Angew Chem Int Ed Engl 1991;30:1387-1391.
220. Wittman MD, Kadow JF, Langley DR, Vyas DM, Rose WC, Solomon W, Zein N. The synthesis and biological activity of enediyne minor groove binding hybrids. Bioorg Med Chem Lett 1995;5:1049-1052.
221. Xie Y, Miller GG, Cubitt SA, Soderlind KJ, Allalunis-Turner MJ, Lown JW. Enediyne-lexitropsin DNA-targeted anticancer agents. Physicochemical and cytotoxic properties in human neoplastic cells in vitro, and intracellular distribution. Anti-Cancer Drug Design 1997;12:169-179.
222. Ji Z, Wang H-K, Bastow KF, Zhu X-K, Cho SJ, Cheng Y-C, Lee K-H. Antitumor agents. 177. Design, synthesis and biological evaluation of novel etoposid analogs bearing pyrrolecarboxamidio group as DNA topoisomerase II inhibitors. Bioorg Med Chem Lett 1997;7:607-612.
223. Zhao R, Al-Said NH, Sternbach DL, Lown JW. Camptothecin and Minor-Groove binder hybrid molecules: Synthesis, inhibition of topoisomerase I and anticancer cytotoxicity in vitro. J Med Chem 1997;40:216-225.
224. Dudiuit FD, Goossens J-F, Houssin R, Henichart J-P, Colson P, Houssier C, Gelus N, Bailly C. Synthesis, DNA binding, topoisomerases inhibition and cytotoxic properties of 4-arylmcarboxamidopyrrolo-2-carboxyanilides. Bioorg Med Chem Lett 2000;10:553-557.
225. Paz MM, Das A, Tomasz M. Mitomycin C linked to DNA minor groove binding agents: Synthesis, reductive activation, DNA binding and cross-linking properties and in vitro antitumor activity. Bioorg Med Chem 1999;7:2713-2726.
226. Helissey P, Giorni-Renault S, Colson P, Houssier C, Bailly C. Sequence-recognition and cleavage of DNA by a netropsin-phenazine-di-N-oxide conjugate. Bioconjugate Chem 2000;11:219-227.
227. Rastogi K, Chang J-Y, Pan W-Y, Chen C-H, Chou T-C, Chen L-T, Su T-L. Antitumor AHMA linked to DNA minor groove binding agents: Synthesis and biological evaluation. J Med Chem 2002;45:4485-4493.
228. Baraldi PG, Cacciari B, Guiotto A, Leoni A, Romagnoli R, Spalluto G, Mongelli N, Thurston DE, Bianchi N, Gambari R. Design, synthesis and biological activity of pyrrolo[2,1-c] [1,4]benzodiazepine (PBD)-distamycin hybrid. Bioorg Med Chem Lett 1998;8:3019-3024.
229. Baraldi PG, Balboni G, Cacciari B, Guiotto A, Manfredini S, Romagnoli R, Spalluto G, Howard PH, Thurston DE, Bianchi N, Rutigliano C, Mischiati C, Gambari R. Synthesis, antiproliferative activity and DNA-binding properties of hybrid molecules containing pyrrolo [2,1-c] [1,4] benzodiazepine (PBD) and minor groove binding. J Med Chem 1999;42:5131-5141.
230. Damayanthi Y, Praveen Reddy BS, Lown JW. Design and synthesis of novel pyrrolo [2,1-c] [1,4] benzodiazepine-lexitropsin conjugates. J Org Chem 1999;64:290-292.
231. Baraldi PG, Cacciari B, Guiotto A, Romagnoli R, Spalluto G, Leoni A, Bianchi N, Feriotto G, Rutigliano C, Mischiati C, Gambari R. [2,1-c] [1,4] benzodiazepine (PBD)-distamycin hybrid inhibits DNA binding to transcription factor Sp1. Nucleos Nucleotides Nucleic Acids 2000;19:1219-1229.
232. Snyder RC, Ray R, Blume S, Miller DM. Mithramycin blocks transcriptional initiation of the c-myc P I and P2 promoters. Biochemistry 1991;30:4290-4297.
233. 1H-NMR and restrained molecular dynamics simulation. J Am Chem Soc 1995;117:8917-8925.
234. Wang Y, Gupta R, Huang L, Luo W, Lown JW. Design, synthesis, cytotoxic properties and preliminary DNA sequencing evaluation of CPI-N-methylpyrrole hybrids. Enhancing effect of a trans double bond linker and role of terminal amide functionality on cytotoxic potency. Anti-Cancer Drug Design 1996; 11:15-34.
235. Baraldi PG, Balboni G, Pavani MG, Spalluto G, Tabrizi MA, De Clercq E, Balzarini J, Bando T, Sugiyama H, Romagnoli R. Design, synthesis, DNA binding and biological evaluation of water-soluble hybrid molecules containing two pyrazole analogues of the alkylating cyclopropylpyrroleindole (CPI) subunit of the antitumor agent CC-1065 and polypyrrole minor groove binders. J Med Chem 2001;44:2536-2543.
236. Toth JL, Price CA, Madsen CA, Handl HL, Hudson SJ, Hubbard RB III, Bowen JP, Kiakos KK, Hartley JA, Lee M. Sequence selective recognition of DNA by hairpin conjugates of a racemic seco-cyclopropaneindoline-2- benzofurancarboxamide and polyamides. Bioorg Med Chem Lett 2002;12:2245-2248.
237. 3H-benz[e]indole (seco-CBI)-pyrrole polyamide conjugates. Org Lett 2002;4:1851-1854.
238. 3H)-one, a novel broad spectrum antitumor agent. J Med Chem 1984;27:196-201.
239. Arrowsmith J, Jennings SA, Clark SA, Stevens MFG. Antitumor imidazotetrazines. 41. Conjugation of the antitumor agents metazolamide and temazolamide to peptides and lexitropsins bearing DNA major and minor groove-binding structural motifs. J Med Chem 2002;45:5458-5470.
240. Zhou Q, Duan W, Simmons D, Shayo Y, Raymond MA, Dorr RT, Hurley LH. Design and synthesis of a novel DNA-DNA interstrand adenine-guanine cross-linking agent. J Am Chem Soc 2001;123:4865-4866.
241. Tercel M, Stribbling SM, Sheppard H, Siim BG, Wu K, Pullen SM, Botting KJ, Wilson WR, Denny WA. Unsymmetrical DNA cross-linking agents: Combination of the CBI and PBD pharmacophores. J Med Chem 2003;46:2132-2151.
242. Kamal A, Reddi BSN, Reddy GSK, Ramesh G. Design and synthesis of C-8 linked pyrrolobenzodiazepine-naphthalimide hybrids as anti-tumor agents. Bioorg Med Chem Lett 2002;12:1933-1935.
243. David-Cordonnier M-H, Laine W, Lansiaux A, Kouach M, Briand G, Pierré A, HiCkman JA, Bailly C. Alkylation of guanine in DNA by S23906-1, a potent antitumor compound derived from the plant alkaloid acronycine. Biochemistry 2002;41:9911-9920.
244. Yamori T, Matsunaga A, Sato S, Yamazaki K, Komi A, Ishizu K, Mita I, Edatsugi H, Matsuba Y, Takezawa K, Nakanishi O, Kohno H, Nakajima Y, Komatsu H, Andoh T, Tsuro T. Potent antitumor activity of MS-247, a novel DNA minor groove binder, evaluated by an in vitro and in vivo human cancer cell line panel. Cancer Res 1999;59:4042-4049.
245. Asai A, Sakai Y, Ogawa H, Yamashita Y, Kakita S, Ochiai K, Ashizawa T, Mihara A, Mizukami T, Nakano H. Pyrronamycin A and B, novel antitumor antibiotics containing pyrrole-amide repeating unit, produced by Streptomyces sp. J Antibiot 2000;53:66-69.