Neglected disease-African sleeping sickness: Recent synthetic and modeling advances

Scientia Pharmaceutica

Volumn 79, Issue 3, 2011, Pages 389-428

  Paliwal, Sarvesh K ^a   Verma, Ankita Narayan ^a   Paliwal, Shailendra ^b  

^a BANASTHALI UNIVERSITY   (India)

^b LLRM MEDICAL COLLEGE   (India)

Author keywords

Central nervous system (CNS); Computer assisted drug design (CADD); Human African trypanosomiasis (HAT); Rypanothione reductase (TR); Structure activity relationship (SAR)

Indexed keywords

1,2 DIHYDRO 2,2,4 TRIMETHIQUINOLIN 6 YL 3,5 DI METHOXYBENZOATE; 3,5 DIPHENYLISOXAZOLE DERIVATIVE; 4 [3 (4 PHENOXYPHENYL) 1H PYRAZOL 5 YL]MORPHOLINE DERIVATIVE; ANTITRYPANOSOMAL AGENT; DNA TOPOISOMERASE INHIBITOR; ETHANE; FURAPROFEN; METHANE; MORPHOLINE; PENTAMIDINE; POLYAMINE METABOLISM INHIBITOR; PYRROLE DERIVATIVE; QUINOLONE DERIVATIVE; TERPHENYL DERIVATIVE; TRYPANOTHIONE REDUCTASE INHIBITOR; UNCLASSIFIED DRUG;

AFRICAN TRYPANOSOMIASIS; COMPUTER ANALYSIS; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG EFFICACY; DRUG POTENCY; DRUG STRUCTURE; HUMAN; MEDICAL RESEARCH; NONHUMAN; REVIEW; STRUCTURE ACTIVITY RELATION;

EID: 80051723101     PISSN: 00368709     EISSN: 22180532     Source Type: Journal    
DOI: 10.3797/scipharm.1012-08     Document Type: Review

References (100)

1. Barrett MP, Burchmore RJS, Stich A, Lazzari JO, Frasch AC, Cazzulo JJ, Krishna S. The trypanosomiases. Lancet. 2003; 362: 1469-1480. doi:10.1016/S0140-6736(03)14694-6
2. African trypanosomiasis. http://www.mscionline.com/projects/diseases/trypano.htm (accessed October 2006).
3. African trypanosomiasis (sleeping sickness). http://www.who.int/mediacentre/factsheets/fs259/en/ (accessed October 2006).
4. Barrett MP. The fall and rise of sleeping sickness. Lancet 1999; 353: 1113-1114. doi:10.1016/S0140-6736(98)00416-4
5. Legros D, Ollivier G, Gastellu-Etchegorry M, Paquet C, Burri C, Jannin J, Buscher P. Treatment of human African trypanosomiasis- present situation and needs for research and development. Lancet Infect Dis. 2002; 2: 437-440. doi:10.1016/S1473-3099(02)00321-3
6. Fairlamb AH. Chemotherapy of human African trypanosomiasis: current and future prospects. Trends Parasitol. 2003; 19: 488-494. doi:10.1016/j.pt.2003.09.002
7. Burri C, Brun R. Human African Trypanosomiasis. Cook GC, Zumla A, editors. In Manson's Tropical Diseases. W. B. Saunders. London. 2003: 1303-1323.
8. Burchmore RJ, Ogbunude PO, Enanga B, Barrett MP. Chemotherapy of human African trypanosomiasis. Curr Pharm Des. 2002; 8: 257-267. doi:10.2174/1381612023396159
9. Docampo R, Moreno SN. Current chemotherapy of human African trypanosomiasis. Parasitol Res. 2003; 90 (Supp 1): S10-S13. doi:10.1007/s00436-002-0752-y
10. Paliwal S, Narayan A, Paliwal S. Quantitative Structure Activity Relationship Analysis of Dicationic Diphenylisoxazole as Potent Anti-Trypanosomal Agents. QSAR Comb Sci. 2009; 28:1367-1375. doi:10.1002/qsar.200860206.
11. da Cunha EFF, Ramalho TC, Mancini DT, Fonseca EMB, Oliveira AA. New Approaches to the Development of Anti-Protozoan Drug Candidates: a Review of Patents. J Braz Chem Soc. 2010; 21: 1787-1806. doi:10.1590/S0103-50532010001000002
12. Tidwell RR, Boykin DW. Dicationic DNA Minor Groove Binders as Antimicrobial Agents. Demeunynck M, Bailly C, Wilson WD, editors. In Small Molecule DNA and RNA Binders; From Synthesis to Nucleic Acid Complexes. Wiley-VCH, New York: 2003: 414. doi:10.1002/3527601783.ch16
13. Bouteille B, Oukem O, Bisser S, Dumas M. Treatment perspectives for human African trypanosomiasis. Fundam Clin Pharmacol. 2003; 17: 171-181. doi:10.1046/j.1472-8206.2003.00167.x
14. Singh H, Sivakumar R. Challenges and new discoveries in the treatment of leishmaniasis. J Infect Chemother. 2004; 10: 307-315. doi:10.1007/s10156-004-0348-9
15. Jannin J, Cattand P. Treatment and control of human African trypanosomiasis. Curr Opin Infect Dis. 2004; 17: 565-571. doi:10.1097/00001432-200412000-00009
16. Barrett MP, Fairlamb AH. The biochemical basis of arsenicaldiamidine crossresistance in African trypanosomes. Parasitol Today. 1999; 15: 136-140. doi:10.1016/S0169-4758(99)01414-3
17. de Koning HP. Transporters in African trypanosomes: role in drug action and resistance. Int J Parasitol. 2001; 31: 512-522. doi:10.1016/S0020-7519(01)00167-9
18. de Koning HP, Jarvis SM. Adenosine transporters in bloodstream forms of Trypanosoma brucei brucei: Substrate recognition motifs and affinity for trypanocidal drugs. Mol Pharmacol. 1999; 56: 1162-1170. PMid:10570043
19. Carter NS, Barrett MP, de Koning HP. A drug resistance determinant in Trypanosoma brucei. Trends Microbiol. 1999; 7: 469-471. doi:10.1016/S0966-842X(99)01643-1
20. Zhang X, Berger BJ, Ulrich P. Synthesis and trypanocidal activity of the bis-carba analogue of pentamidine. Bioorg Med Chem Lett. 1996; 6: 1035-1036. doi:10.1016/0960-894X(96)00168-0
21. Bell CA, Hall JE, Kyle DE, Grogl M, Ohemeng KA, Allen MA,Tidwell RR. Structure-activity relationships of analogs of pentamidine against Plasmodium falciparum and Leishmania mexicana amazonensis. Antimicrob Agents Chemother. 1990; 34: 1381-1386.PMid:2201254
22. Tidwell RR, Jones SK, Geratz JD, Ohemeng KA, Cory M, Hall JE. Analogues of 1,5-bis(4-amidinophenoxy)pentane (pentamidine) in the treatment of experimental Pneumocystis carinii pneumonia. J Med Chem. 1990; 33: 1252-1257. doi:10.1021/jm00166a026
23. Donkor IO, Huang TL, Tao B, Rattendi D, Lane S, Vargas M, Goldberg B, Bacchi C. Trypanocidal activity of conformationally restricted pentamidine congeners. J Med Chem. 2003; 46: 1041-1048. DOI: 10.1021/jm020375q
24. Bakunova SM, Bakunov SA, Patrick DA, Kumar SEVK, Ohemeng KA, Bridges AS, Wenzler T, Barszcz T, Jones SK, Werbovetz KA, Brun R, Tidwell RR. Structure-activity study of pentamidine analogues as antiprotozoal agents. J Med Chem. 2009; 52: 2016-2035. doi:10.1021/jm801547t
25. Das BP, Boykin DW. Synthesis and antiprotozoal activity of 2,5-bis(4-guanylphenyl)furans. J Med Chem. 1977; 20: 531-536 doi:10.1021/jm00214a014
26. Ismail MA, Brun R, Easterbrook JD, Tanious FA, Wilson WD, Boykin DW. Synthesis and antiprotozoal activity of aza-analogues of furamidine. J Med Chem. 2003; 46: 4761-4769. doi:10.1021/jm0302602
27. Mathis AM, Holman JL, Sturk LM, Ismail MA, Boykin DW, Tidwell RR, Hall JE. Accumulation and intracellular distribution of anti-trypanosomal diamidine compounds DB75 and DB820 in African trypanosomes. Antimicrob Agents Chemother. 2006; 50: 2185-2191. doi:10.1128/AAC.00192-06
28. Bakunova SM, Bakunov SA, Wenzler T, Barszcz T, Werbovetz KA, Brun R, Tidwell RR. Synthesis and Antiprotozoal Activity of Pyridyl Analogues of Pentamidine. J Med Chem. 2009; 52: 4657-4667. doi:10.1021/jm900805v
29. Baliani A, Bueno GJ, Stewart ML, Yardley V, Brun R, Barrett MP, Gilbert IH. Design and synthesis of a series of melamine-based nitroheterocycles with activity against Trypanosomatid parasites. J Med Chem. 2005; 48: 5570-5579. doi:10.1021/jm050177+
30. Dann O, Fernbach R, Pfeifer W, Demant E, Bergen G, Lang S, Lurding G. Trypanocide Diamidine mit drei Ringen in zwei isolierten Ringsystemen. Liebigs Ann Chem. 1972; 760: 37-87. doi:10.1002/jlac.19727600105
31. Dann O, Volz G, Demant E, Pfeifer W, Bergen G, Fick H, Walkenhorst E. Trypanocide Diamidine mit vier Ringen in einem oder zwei Ringsystemen. Liebigs Ann Chem. 1973; 1112-1140. doi:10.1002/jlac.197319730708
32. Dann O, Char H, Griebmeier H. Synthesen biskationischer, trypanocider 1-Benzofuran-verbindungen. Liebigs Ann Chem. 1982; 1836-1869. doi:10.1002/jlac.198219821008
33. Bakunova SM, Bakunov SA, Wenzler T, Barszcz T, Werbovetz KA, Brun R, Hall JE, Tidwell RR. Synthesis and in vitro Antiprotozoal Activity of Bisbenzofuran Cations. J Med Chem. 2007; 50: 5807-5823. doi:10.1021/jm0708634
34. Bakunov SA, Svetlana M, Bakunova SM, Wenzler T, Barszcz T, Werbovetz KA, Brun R, Tidwell RR. Synthesis and Antiprotozoal Activity of Cationic 2-Phenylbenzofurans. J Med Chem. 2008; 51: 6927-6944. doi:10.1021/jm800918v
35. Bakunova SM, Bakunov SA, Bridges SA, WenzlerT, Barszcz T, Werbovetz KA, Brun R, Tidwell RR. Synthesis and Antiprotozoal Properties of Pentamidine Congeners Bearing the Benzofuran Motif. J Med Chem. 2009; 52: 5763-5767. doi:10.1021/jm9006406
36. Yeates C. DB-289 Immtech International. IDrugs 2003; 6: 1086-1093. PMid:14600842
37. Das BP, Boykin DW. Synthesis and antiprotozoal activity of 2, 5-bis(4-guanylphenyl)furans. J Med Chem. 1977; 20: 1219-1221. doi:10.1021/jm00219a023
38. Das BP, Wallace R A, Boykin DW. Synthesis and anti-trypanosomal activity of some bis(4-guanylphenyl) five- and six-membered ring heterocycles. J Med Chem. 1980; 23: 578-581. doi:10.1021/jm00179a022
39. Boykin DW, Kumar A, Baji M, Xiao G, Wilson WD, Bender BC, McCurdy DR, Hall JE, Tidwell RR. Anti-Pneumocystis carinii pneumonia activity of dicationic diaryl methylpyrimidines. Eur J Med Chem. 1997; 32: 965-972. doi:10.1016/S0223-5234(97)89640-7
40. Spychala J, Boykin DW, Wilson WD, Zhao M, Tidwell RR, Dykstra CC, Hall JE, Jones SK, Schinazi RF. Synthesis of dicationic diaryltriazines nucleic acid binding agents. Eur J Med Chem. 1994; 29: 363-367. doi:10.1016/0223-5234(94)90061-2
41. Francesconi I, Wilson WD, Tanious FA, Hall JE, Bender BC, Tidwell RR, McCurdy DR, Boykin DW. 2,4-Diphenylfurandiamidines as novel anti-Pneumocystis carinii pneumonia agents. J Med Chem. 1999; 42: 2260-2265. doi:10.1021/jm990071c
42. Dann O, Fick H, Peitzner B, Walkenhorst E, Fernbach R, Zeh D. Trypanocidal diamidines with three isolated ring systems. Liebigs Ann Chem. 1975; 160-194. doi:10.1002/jlac.197519750115
43. Patrick DA, Bakunov SA, Bakunova SM, Kumar EVKS, Lombardy RJ, Jones SK, Bridges AS, Zhirnov O, Hall JE, Wenzler T, Brun R, Tidwell RR. Synthesis and in vitro Antiprotozoal Activities of Dicationic 3,5-Diphenylisoxazoles. J Med Chem. 2007; 50: 2468-2485.
44. Bakunova SM, Bakunov SA, Wenzler T, Ghebru M, Werbovetz KA, Brun R, Tidwell RR. Synthesis and Antiprotozoal Activity of Cationic 1,4-Diphenyl-1H-1,2,3-triazoles. J Med Chem. 2010; 53: 254-272.
45. Biagi G, Livi O, Ramacciotti GL, Scartoni V, Bazzichi L, Mazzoni MR, Lucacchini A. Superoxide dismutase-like activity of 1, 2, 3-triazole derivatives. Farmaco. 1990; 45: 49-57. PMid:2337447
46. Wadsworth HJ, Jenkins SM, Orlek BS, Cassidy F, Clark MS, Brown F, Riley GJ, Graves D, Hawkins J, Naylor CB. Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives. J Med Chem. 1992; 35: 1280-1290. doi:10.1021/jm00085a016
47. Savini L, Massarelli P, Corti P, Chiasserini L, Pellerano C, Bruni G. New 1-[quinolyl(4)]-1,2,3-triazoles: synthesis and evaluation of antiinflammatory and analgesic properties I. Farmaco. 1994; 49: 363-369. PMid:8080620
48. Savini L, Massarelli P, Chiasserini L, Pellerano C, Bruni G. New 1-[quinolyl(4)]-1,2,3-triazoles: synthesis and evaluation of antiinflammatory and analgesic properties II. Farmaco 1994; 49: 633-639. PMid:7826469
49. Moltzen EK, Pedersen H, Bogeso KP, Meier E, Frederiksen K, Sanchez C, Love LH. Bioisosteres of arecoline: 1,2,3,6- tetrahydro-5-pyridyl-substituted and 3-piperidyl-substituted derivatives of tetrazoles and 1,2,3-triazoles. Synthesis and muscarinic activity. J Med Chem. 1994; 37: 4085-4099. doi:10.1021/jm00050a006
50. Kim DK, Kim J, Park HJ. Synthesis and biological evaluation f novel 2-pyridinyl-[1,2,3]triazoles as inhibitors of transforming rowth factor beta 1 type 1 receptor. Bioorg Med Chem Lett. 2004; 14: 2401-2405. doi:10.1016/j.bmcl.2004.03.024
51. Whiting M, Tripp JC, Lin YC, Lindstrom W, Olson AJ, lder JH, Sharpless KB, Fokin VV. Rapid discovery and structure-activity profiling of novel inhibitors of human immunodeficiency irus type 1 protease enabled by the copper(I)-catalyzed synthesis of 1,2,3-triazoles and their further functionalization. J Med Chem. 2006; 49: 7697-7710. doi:10.1021/jm060754+
52. Cheng ZY, Li WJ, He F, Zhou JM, Zhu XF. Synthesis and biological evaluation of 4-aryl-5-cyano-2H-1, 2, 3-triazoles as inhibitor of HER2 tyrosine kinase. Bioorg Med Chem 2007; 5: 1533-1538. doi:10.1016/j.bmc.2006.09.041
53. da Silva FC, de Souza MC, Frugulhetti II, Castro HC, Souza SL, de Souza TM, Rodrigues DQ, Souza AM, Abreu PA, Passamani F, Rodrigues CR, Ferreira VF. Synthesis, HIV-RT inhibitory activity and SAR of 1-benzyl-1H- 1, 2, 3-triazole derivatives of carbohydrates. Eur J Med Chem. 2009; 44: 373-383. doi:10.1016/j.ejmech.2008.02.047
54. Hou DR, Alam S, Kuan TC, Ramanathan M, Lin TP, Hung MS. 1,2,3-Triazole derivatives as new cannabinoid CB1 receptor antagonists. Bioorg Med Chem Lett. 2009; 19: 1022-1025. doi:10.1016/j.bmcl.2008.11.029
55. Shu H, Izenwasser S, Wade D, Stevens ED, Trudell ML. Synthesis and CB1 cannabinoid receptor affinity of 4-alkoxycarbonyl-1,5-diaryl-1,2,3-triazoles. Bioorg Med Chem Lett. 2009; 19: 891-893. doi:10.1016/j.bmcl.2008.11.110
56. Donkor IO, Huang TL, Tao B, Rattendi D, Lane S, Vargas M, Goldberg B, Bacchi C. Trypanocidal activity of conformationally restricted pentamidine congeners. J Med Chem. 2003; 46: 1041-1048. doi:10.1021/jm020375q
57. Rodríguez F, Rozas I, Marcel K, Brun R, Nguyen B, Wilson WD, Nelson RG, Dardonville C. New Bis(2-aminoimidazoline) and Bisguanidine DNA Minor Groove Binders with Potent in vivo Anti-trypanosomal and Antiplasmodial Activity. J Med Chem. 2008; 51: 909-923. doi:10.1021/jm7013088
58. Dardonville C, Barrett MP, Brun R, Kaiser M, Tanious F, Wilson WD. DNA binding affinity of bisguanidine and bis(2- aminoimidazoline) derivatives with in vivo anti-trypanosomal activity. J Med Chem. 2006; 49: 3748-3752. doi:10.1021/jm060295c
59. Dardonville C, Brun R. Bisguanidine, bis(2-aminoimidazoline), and polyamine derivatives as potent and selective chemotherapeutic agents against Trypanosoma brucei rhodesiense. Synthesis and in vitro evaluation. J Med Chem. 2004; 47: 2296-2307. doi:10.1021/jm031024u
60. Spinks D, Shanks EJ, Cleghorn LAT, McElroy S, Jones D, James D, Fairlamb AH, Frearson JA, Wyatt PG, Gilbert IH. Investigation of Tryoanothione reductase as a target in Trypanosoma brucei. ChemMedChem. 2009; 4: 2060-2069. doi:10.1002/cmdc.200900262
61. Jean F, Kaiser M, Delfine DA, Manley J, Reid CS, Paris JM, Wenzler T, Maes L, Mahasenan KV, Li C, Werbovetz KA. Anti-trypanosomal Activity of 1,2-Dihydroquinolin-6-ols and Their Ester Derivatives. J Med Chem. 2010; 53: 966-982. doi:10.1021/jm900723w
62. Bakshi RP, Sang D, Morrell A, Cushman M, Shapiro TA. Activity of Indenoisoquinolines against African Trypanosomes. Antimicrob Agents Chemother. 2009; 123-128. doi:10.1128/AAC.00650-07
63. Keiser J, Burri C. Evaluation of quinolone derivatives for anti-trypanosomal activity. Trop Med Int Health. 2001; 6: 369-389. doi:10.1046/j.1365-3156.2001.00713.x
64. Karigiannis G, Papaioannou D. Structure, Biological Activity and Synthesis of Polyamine Analogues and Conjugates. Eur J Org Chem. 2000; 1841-1863. doi:10.1002/(SICI)1099-0690(200005)2000:10<1841::AID-EJOC1841>3.0.CO;2-9
65. Kuksa V, Buchan R, Lin PKT. Synthesis of Polyamines, Their Derivatives, Analogues and Conjugates. Synthesis. 2000; 1189-1207. doi:10.1055/s-2000-6405
66. Tabor CW, Tabor H. Polyamines. Annu Rev Biochem. 1984; 53: 749-790. doi:10.1146/annurev.bi.53.070184.003533
67. Marton LJ, Pegg AE. Polyamines as Targets for Therapeutic Intervention. Annu Rev Pharmacol Toxicol. 1995; 35: 55-91. doi:10.1146/annurev.pa.35.040195.000415
68. Hide G, Mottram JC, Coombs GH, Holmes PH. Trypanosomiasis and Leishmaniasis: Biology and Control. CAB International: Oxon: 1997.
69. Phillips MA, Coffino P, Wang CC. Trypanosoma Brucei Ornithine Decarboxylase - Enzyme Purification, Characterization, and Expression in Escherichia-Coli. J Biol Chem. 1988; 263: 17933-17941. PMid:3056933
70. Bacchi CJ, Nathan HC, Hutner SH, McCann PP, Sjoerdsma A. Polyamine metabolism: a potential therapeutic target in trypanosomes. Science. 1980; 210:332-334. doi:10.1126/science.6775372
71. Nieuwenhove SV. Advances in sleeping sickness therapy. Ann Soc Belg Med Trop. 1992; 72 (Suppl 1): 39-51. PMid:1417168
72. Priotto G, Pinoges L, Fursa, IB, Burke B, Nicolay N, Grillet G, Hewison C, Balasegaram M. Safety and effectiveness of first line eflornithine for Trypanosoma brucei gambiense sleeping sickness in Sudan: cohort study. Br Med J. 2008; 336: 705-708. doi:10.1136/bmj.39485.592674.BE
73. Priotto G, Fogg C, Balasegaram M, Erphas O, Louga A, Checchi F, Ghabri S, Piola P. Three drug combinations for late-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Uganda. PLoS Clin Trials 2006; 1: 1-8. doi:10.1371/journal.pctr.0010001
74. Priotto G, Kasparian S, Ngouama D, Ghorashian S, Arnold U, Ghabr S, Karunakara U. Nifurtimox eflornithine combination therapy for second-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Congo. Clin Infect Dis. 2007; 45: 1435-1442. doi:10.1086/522982
75. Bitonti AJ, Byers TL, Bush TL, Casara PJ, Bacchi CJ, Clarkson AB, McCann PP, Sjoerdsma A. Cure of Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense infections in mice with an irreversible inhibitor of S-adenosylmethionine. Antimicrob Agents Chemother. 1990; 34: 1485-1490. PMid:1977366
76. Klenke B, Stewart M, Barrett MP, Brun R, Gilbert IH. Synthesis and Biological Evaluation of s-Triazine Substituted Polyamines as Potential New Anti-Trypanosomal Drugs. J Med Chem. 2001; 44: 3440-3452. doi:10.1021/jm010854+
77. Rapp M, Haubrich TA, Perrault J, Mackey ZB, McKerrow JH, Chiang PK, Wnuk SF. Anti-trypanosomal Activity of 5'-Deoxy-5'-(iodomethylene) adenosine and Related 6-N-Cyclopropyladenosine Analogues. J Med Chem. 2006; 49: 2096-2102. doi:10.1021/jm0511379
78. Wnuk SF, Yuan CS, Borchardt RT, Balzarini J, De Clercq E, Robins MJ. Synthesis of 6' (E and Z)-halohomovinyl derivatives of adenosine, inactivation of S-adenosyl-L-homocysteine hydrolase, and correlation of anticancer and antiviral potencies with enzyme inhibition. J Med Chem. 1994; 37: 3579-3587. doi:10.1021/jm00047a015
79. Bujnicki JM, Prigge ST, Caridha D, Chiang PK. Structure, evolution, and inhibitor interaction of S-adenosyl-L-homocysteine hydrolase from Plasmodium falciparum. Protein. 2003; 52: 624-632. doi:10.1002/prot.10446
80. Kuettel S, Zambon A, Kaiser M, Brun R, Scapozza L, Perozzo R. Synthesis and Evaluation of Antiparasitic Activities of New 4-[5-(4-Phenoxyphenyl)-2H-pyrazol-3-yl] morpholine Derivatives. J Med Chem. 2007; 50: 5833-5839. doi:10.1021/jm700938n
81. D'Silva C, Daunes S. Structure-Activity Study on the in vitro Antiprotozoal Activity of Glutathione Derivatives. J Med Chem. 2000; 43: 2072-2078. doi:10.1021/jm990259w
82. Boykin DW, Kumar A, Spychala J, Zhou M, Lombardy RL, Wilson WD, Dykstra CC, Jones SK, Hall JE, Tidwell RR, Laughton C, Nunn CM, Neidle S. Dicationic Diaryl Furans as Anti-Pneumocystis carinii Agents. J Med Chem. 1995; 38: 912-916. doi:10.1021/jm00006a009
83. Hall JE, Kerrigan JE, Ramachandran K, Bender BC, Stanko JP, Jones SK, Patrick DA Tidwell RR. Anti-Pneumocystis Activity of Aromatic Diamidoxime Prodrugs. Antimicrob Agents Chemother. 1998; 42: 666-674. PMid:9517949
84. Boykin DW, Kumar A, Xiao G, Wilson WD, Bender BC, McCurdy DR, Hall JE, Tidwell RR. 2,5-Bis[4-(N-alkylamidino)phenyl]furans as Pneumocystis carinii Agents. J Med Chem. 1998; 41: 124-129. doi:10.1021/jm970570i
85. Ansede JH, Anbazhagan M, Brun R, Easterbrook JD, Hall JE, Boykin DW. O-Alkoxyamidine Prodrugs of Furamidine: In vitro Transport and Microsomal Metabolism as Indicators of in vivo Efficacy in a Mouse Model of Trypanosoma brucei rhodesiense Infection. J Med Chem. 2004; 47: 4335-4338. doi:10.1021/jm030604o
86. Ismail MA, Arafa RK, Brun R, Wenzler T, Miao Y, Wilson WD, Generaux C, Bridges A, Hall JE, Boykin DW. Synthesis, DNA Affinity, and Antiprotozoal Activity of Linear Dications: Terphenyl Diamidines and Analogues. J Med Chem. 2006; 49: 5324-5332. doi:10.1021/jm060470p
87. Arafa RK, Brun R, Wenzler T, Tanious FA, Wilson WD, Stephens CE, Boykin DW. Synthesis, DNA Affinity, and Antiprotozoal Activity of Fused Ring Dicationic Compounds and Their Prodrugs. J Med Chem. 2005; 48: 5480-5488. doi:10.1021/jm058190h
88. Rahmathullah SM, Hall JE, Brender BC, McCurdy DR, Tidwell RR, Boykin DW. Prodrugs for Amidines: Synthesis and Anti-Pneumocystis carinii Activity of Carbamates of 2,5-Bis-[4-amidinophenyl]furan. J Med Chem. 1999; 42: 3994-4000. doi:10.1021/jm990237+
89. Itzstein VM, Wu WY, Kok GB. Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature. 1993; 363: 418-423. doi:10.1038/363418a0
90. Melnick M, Reich SH, Lewis KK. Bis tertiary amide inhibitors of the HIV-1 protease generated via protein structure-based iterative design. J Med Chem. 1996; 39: 2795-2811. doi:10.1021/jm960092w
91. Ring CS, Sun E, McKerrow JH. Structure-based inhibitor design by using protein models for the development of antiparasitic agents. Proc Natl Acad Sci U S A. 1993; 90: 3583-3587. doi:10.1073/pnas.90.8.3583
92. Hibert MF, Hoffmann R, Miller RC. Conformation-activity relationship study of 5-HT3 receptor antagonists and a definition of a model for this receptor site. J Med Chem. 1990; 33: 1594-1600. doi:10.1021/jm00168a011
93. Motoc I, Sit SY, Harte WE. 3-Hydroxy-3-methylglutaryl-coenzyme. A reductase: Molecular modeling, three-dimensional structure-activity relationships, inhibitor design. Quant Struct Act Relat. 1991; 10: 30-35. doi:10.1002/qsar.19910100106
94. Xiong B, Gui CS, Xu XY, Luo C, Chen J, Luo HB, Chen LL, Li GW, Sun T, Yu CY, Yue LD, Duan WH, Shen JK, Qin L, Shi TL, Li YX, Chen KX, Luo XM, Shen X, Shen JH, Jiang HL. A 3D model of SARS-CoV 3CL proteinase and its inhibitors design by virtual screening. Acta Pharmacol Sin. 2003; 24: 497-504. PMid:12791174
95. Pastor M, Cruciani G. A novel strategy for improving ligand selectivity in receptor-based drug design. J Med Chem. 1995; 38: 4637-4647. doi:10.1021/jm00023a003
96. Anand, K, Ziebuhr J, Wadhwani P, Mesters JR, Hilgenfeld R. Corona virus main proteinase (3CLpro) Structure: Basis for design of anti-SARS drugs. Science. 2003; 300: 1763-1767. doi:10.1126/science.1085658
97. Hansch C, Mahoney PP, Fujita T, Muir RM. Correlation of biological activity of phenoxyacetic acids with Hammett substituent constants and partition coefficients. Nature. 1962; 194: 178-180. doi:10.1038/194178b0
98. Athri P, Wenzler T, Ruiz P, Brun R, Boykin DW,Tidwell RR, Wilson WD. 3D QSAR on a library of heterocyclic diamidine derivatives with antiparasitic activity. Bioorg Med Chem. 2006; 14: 3144-3152. doi:10.1016/j.bmc.2005.12.029
99. Martin MB, Sanders JM, Kendrick H, Fradley K, Lewis CJ, Grimley J, S Erin M Van Brussel, Olsen JR, Meints GA, Burzynska A, Kafarski P, Croft SL, Oldfield E. Activity of Bisphosphonates against Trypanosoma brucei rhodesiense. J Med Chem. 2002; 45: 2904-2914. doi:10.1021/jm0102809
100. Daunes S, D'Silva C, Kendrick H, Yardley V, Croft SL. QSAR Study on the Contribution of Log P and Es to the in vitro Antiprotozoal Activity of Glutathione Derivatives. J Med Chem. 2001; 44: 2976-2983. doi:10.1021/jm000502n