Structure-antileukemic activity relationship study of B- and D-ring modified and nonmodified steroidal esters of 4-methyl-3-N,N-bis(2-chloroethyl) amino benzoic acid: A comparative study

Anti-Cancer Drugs

Volumn 18, Issue 9, 2007, Pages 997-1004

  Fousteris, Manolis A ^a,d   Koutsourea, Anna I ^a   Arsenou, Evagelia S ^a   Papageorgiou, Athanasios ^b   Mourelatos, Dionysios ^c   Nikolaropoulos, Sotiris S ^a  

^a UNIVERSITY OF PATRAS   (Greece)

^b Theagenion Anticancer Institute

^c ARISTOTLE UNIVERSITY OF THESSALONIKI   (Greece)

^d UNIVERSITY OF PATRAS   (Greece)

Author keywords

7 keto 5 steroids; Antileukemic activity; B steroidal lactams; D steroidal lactams; Steroidal esters; Structure activity relationship

Indexed keywords

4 METHYL 3 N,N BIS(2 CHLOROETHYL)AMINO BENZOIC ACID; ANTILEUKEMIC AGENT; BENZOIC ACID DERIVATIVE; BETA LACTAMASE; CHLORAMBUCIL; CHLORMETHINE; ESTER; ESTERASE; PHENYLACETIC ACID; STEROID; UNCLASSIFIED DRUG;

ALKYLATION; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER INHIBITION; CELL CYCLE ARREST; CELL DIVISION; CHEMICAL BOND; COMPARATIVE STUDY; CONTROLLED STUDY; DNA DAMAGE; DRUG MECHANISM; FEMALE; HUMAN; HUMAN CELL; LEUKEMIA; LYMPHOCYTE; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION; TUMOR GROWTH;

4-AMINOBENZOIC ACID; ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL PROLIFERATION; ESTERS; FEMALE; LETHAL DOSE 50; LEUKEMIA L1210; LEUKEMIA P388; MALE; MICE; MICE, INBRED STRAINS; MOLECULAR STRUCTURE; SISTER CHROMATID EXCHANGE; STEROIDS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 34548095907     PISSN: 09594973     EISSN: None     Source Type: Journal    
DOI: 10.1097/CAD.0b013e3281822629     Document Type: Article

References (49)

1. Hurley LH. DNA and its associated processes as targets for cancer therapy. Nat Rev Cancer 2002; 2:188-200.
2. DeVita VT, Hellman S, Rosenberg SA. Cancer: principles and practice of ongology. 6th ed. Philadelphia: Lippincott-Raven; 2001.
3. Prakash AS, Valu KK, Wakelin LPG, Woodgate PD, Denny WA. Synthesis and antitumor activity of the spatially separated mustard bis-N,N′-[3- (N-(2-chloroethyl)-N-ethyl) amino-5-((N,N-dimethylamino) methyl)amino-phenyl] 1,4-benzenedi carboxamide, which alkylates DNA exclusively at adenines in the minor groove. Anti-Cancer Drug Des 1991; 6:195-206.
4. Lee M, Rhodes AL, Wyatt MD, Forrow S, Hartley JA. Design, synthesis and biological evaluation of DNA sequence and minor groove selective alkylating agents. Anti-Cancer Drug Des 1993; 8:173-192.
5. Baraldi PG, Romagnoli R, Bianchi N, Gambari R. Benzoyl nitrogen mustard derivatives of benzoheterocyclic analogues of netropsin: synthesis and biological activity. Biorg Med Chem 2003; 11:2381-2388.
6. Papot S, Combaud D, Bosslet K, Gerken M, Crech J, Gesson J-P. Synthesis and cytotoxic activity of a glucuronylated prodrug of nornitrogen mustard. Biorg Med Chem Lett 2000; 10:1835-1837.
7. Lippman M, Bolan G, Huff K. The effects of adrogens and antiadrogens on hormone-responsive human breast cancer in long-term tissue culture. Cancer Res 1976; 36:4610-4618.
8. Martin JD, Hahnel R, McCartney AJ, Woolings TL. The effect of estrogen status on survival in patients with endometrial cancer. Am J Obstet Gynecol 1983; 147:322-324.
9. Sica V, Nola E, Contieri E, Bova R, Manucci MT, Medici N, et al. Estradiol and progesterone receptors in malignant gastrointestinal tumors. Cancer Res 1984; 44:4670-4674.
10. Haveman K, Massberg M, Rotch M. Possible role of androgens in small cell lung cancer (SCLC). J Cancer Res Clin Ongol 1989; 115 (Suppl):30 CE 27.
11. Rank P, Peter R, Depenbrock H, Eisenbrand G, Schmid P, Pitzl H, Hanauske A-R. Preclinical activity of 17β-[N-[N′-(2-chloroethyl) -N′-nitrosocarbamoyl] L-alanyl]-5α-dihydrotestosterone (E91) against tumour colony forming units and heamatopoietic progenitor cells. Eur J Cancer 1999; 35:1009-1013.
12. Albrecht W, Van Poppel H, Horenlas S, Mickisch G, Horwich A, Secretta V, et al. Randomized phase II trial assessing estramustine and vinblastine combination chemotherapy vs estramustine alone in patients with progressive hormone-escaped metastatic prostate cancer. Br J Cancer 2004; 90:100-105.
13. Brandt L, Konyves I, Moller TR. Therapeutic effect of LEO 1031, an alkylating corticosteroid ester, in lymphoprolifarative disorders. I. Chronic lymphocytic leukemia. Acta Med Scand 1975; 197:317-322.
14. Eisenbrand G, Berger MR, Brix HP, Muhlbauer K, Nowrousian MR, Przybilski M, et al. Nitrosoureas. Modes of action and prespectives in the use of hormone affinity carrier molecules. Acta Oncol 1989; 28:203-211.
15. Brix HP, Berger MR, Schneider MR, Tang WC, Eisenbrand G. Androgen-linked alkylating agents: biological activity in methylnitrosourea-induced rat mammary carcinoma. J Cancer Res Clin Oncol 1990; 116:538-549.
16. Catsoulacos P, Catsoulacos D. Antitumor activity of homo-aza-steroidal esters of p-N,N-bis(2-chloroethyl)aminophenoxyacetic acid. Anticancer Res 1993; 13:1203-1208.
17. Camoutsis C, Sambani C, Trafalis D, Peristeris P. On the formation of steroidal amidoesters of 4-[N,N-bis(2-chloroethyl)amino]benzoic acid and their cytotoxic activity. Eur J Med Chem 1999; 34:645-649.
18. Camoutsis C, Trafalis D. An overview on the antileukemic potential of D-homo-aza- and respective 17-beta-acetamido-steroidal alkylating esters. Invest New Drugs 2003; 21:47-54.
19. Arsenou E, Fousteris M, Koutsourea A, Papageorgiou A, Karayianni V, Mioglou E, et al. The allylic 7-ketone at the steroidal skeleton is crucial for the antileukemic potency of chlorambucil's active metabolite steroidal esters. Anti-Cancer Drugs 2004; 15:983-990.
20. Papageorgiou A, Koutsourea A, Arsenou E, Fousteris E, Mourelatos D, Nikolaropoulos S. Structure-antileukemic activity relationship study of B and D-ring modified and non-modified steroidal esters of chlorambucil's active metabolite. Anticancer Drugs 2005; 16:1075-1082.
21. Mitra K, Marquis JC, Hillier SM, Rye PT, Zayas B, Lee AS, et al. A rationally designed genotoxin that selectively destroys estrogen receptor-positive breast cancer cells. JACS 2002; 124:1862-1863.
22. Sharma U, Marquis JC, Dinaut N, Hillier SM, Fedeles B, Rye PT, et al. Design, synthesis and evaluation of estradiol-linked genotoxicants as anticancer agents. Biorg Med Chem Lett 2004; 14:3829-3833.
23. Marquis JC, Hillier SM, Dinaut AN, Rodrigues D, Mitra K, Essigmann JM, Croy RG. Disruption of gene expression and induction of apoptosis in prostate cancer cells by a DNA-damaging agent tethered to an adrogen receptor ligand. Chem Biol 2005; 12:779-787.
24. Wall ME, Abernethy GS Jr, Caroll FJ, Taylor DJ. The effect of some steroidal alkylating agents on experimental animal mammary tumor and leukemia systems. J Med Chem 1969; 12:810-818.
25. Catsoulacos P, Politis D, Wampler GL. Anew steroidal alkylating agent with improved activity in advanced murine leukemias. Cancer Chemother Pharmacol 1979; 3:67-70.
26. Catsoulacos P, Wampler GL. Activity of 3β-hydroxy-13α-amino- 13,17-seco-5α-androstan-17-oic-13,17-lactam-p-bis(2-chloroethyl) -aminophenylacetate. Oncology 1982; 39:109-112.
27. Karayianni V, Papageorgiou A, Mioglou E, Iakovidou Z, Mourelatos D, Fousteris M, et al. 7-Keto hybrid steroidal esters of nitrogen mustard: cytogenetic and antineoplastic effects. Anti-Cancer Drugs 2002; 13: 637-643.
28. Mc Lean A, Woods RC, Catovsky D, Farmer P. Pharmakokinetics and metabolism of chlorambucil in patients with malignant disease. Cancer Treat Rev 1979; 6 (Suppl):33-42.
29. Pettersson-Fernholm T, Vilpo J, Kosonen M, Hakala K, Hovinen J. Reactions of 4-bis(2-chloroethyl)aminophenylacetic acid (phenylacetic mustard) in physiological solutions. J Chem Soc Perkin Trans 2, 1999; 10:2183-2187.
30. Fousteris M, Koutsourea A, Arsenou E, Papageorgiou A, Mourelatos D, Nikolaropoulos S. Structure-antileukemic activity relationship study of B- and D-ring modified and non-modified steroidal esters of chlorambucil. Anticancer Drugs 2006; 17:511-519.
31. Karayianni V, Mioglou E, Iakovidou Z, Mourelatos D, Fousteris M, Koutsourea A, et al. A new approach for evaluating in vivo anti-leukemic activity using the SCE assay. An application on three newly synthesized anti-tumor steroidal esters. Mutat Res 2003; 535:79-86.
32. Fousteris MA, Koutsourea AI, Arsenou ES, Papageorgiou A, Mourelatos D, Nikolaropoulos S. Antileukemic and cytogenetic effects of modified and nonmodified esteric steroidal derivatives of 4-methyl-3-bis(2-chloroethyl)amino benzoic acid (4-Me-CABA). Anticancer Res 2002; 22:2293-2300.
33. Anastasiou A, Catsoulacos P, Papageorgiou A, Margariti E. On the formation of homo-azasteroidal esters of N,N-bis(2-chloroethyl) aminobenzoic acid isomers and their antitumor activity. J Heterocyclic Chem 1994; 31: 367-373.
34. Regan BM, Hayes FN. 17 and 17α-aza-D-homo steroids. J Am Chem Soc 1956; 78:639-643.
35. 5-steroidal substrates. Steroids 2003; 68:407-414.
36. Koutsourea A, Arsenou E, Fousteris M, Nikolaropoulos S. Synthetic approachs for the synthesis of a cytostatic steroidal B-D bilactam. Steroids 2003; 68:659-666.
37. Nicolescu-Duvaz I, Ionescu M, Cambanis A, Vitan M, Feyns V. Potential anticancer agents. IV. Nitrogen mustards of methylbenzoic acid. J Med Chem 1968; 11:500-503.
38. Cambanis A, Dobre V, Niculescu-Duvaz I. Potential anticancer agents. V. New aromatic nitrogen mustards related to 3-[N,N-bis(2-chloroethyl)amino] -4-methylbenzoic acid. J Med Chem 1969; 12:161-164.
39. Goto K, Maeda S, Kano Y, Sugiyama T. Factors involved in differential Giemsa-staining of sister chromatids. Chromosoma 1978; 66:351-359.
40. Goldin A, Sofina Z, Syrkin A. Experimental evaluation of antitumor drugs in the USA and USSR and clinical correlations. Natl Cancer Inst Monogr 1980; 55:25-26.
41. Panda D, Miller HP, Islam K, Wilson L. Stabilization of microtubule dynamics by estramustine by binding to a novel site in tubulin: a possible mechanistic basis for its antitumor action. Proc Natl Acad Sci U S A 1997; 94:10560-10564.
42. Laing N, Dahlöf B, Harley-Asp B, Ranganathan S, Tew KD. Interaction of estramustine with tubulin isotypes. Biochem 1997; 36:871-878.
43. Nicholson KM, Phillips RM, Shnyder SD, Bibby MC. In vitro and in vivo activity of LS 4477 and LS 4559, novel analogues of the tubulin binder estramustine. Eur J Cancer 2002; 38:194-204.
44. Björk P, Forsgren B, Gustafsson JA, Poustte A, Högberg B. Partial characterization and 'quantitation' of a human prostatic estramustine-binding protein. Cancer Res 1982; 42:1935-1942.
45. Kasal A. Epalons: 6-substituted derivatives of 7-norepiallopregnanolone. Tetrahedron 2000; 56:3559-3565.
46. Deen DF, Kendall LA, Marton LJ, Tofilon P. Prediction of human tumour cell chemosensitivity using the SCE assay. Cancer Res 1986; 46:1599-1602.
47. Mourelatos D. Chromosomes study as predictor of chemoresponse of tumours. Cancer J 1996; 9:136-141.
48. Tolifon P, Basic I, Milas L. Prediction of in vivo tumor response to chemotherapeutic agents by the in vitro SCE assay. Cancer Res 1985; 45:2025-2030.
49. Mourelatos D, Dozi J, Kotsis A, Gourtsas C. Enhancement of cytogenetic damage and of antineoplastic effect by caffeine in Ehrlich ascites tumour cells treated with cyclophosphamide in vivo. Cancer Res 1988; 48: 1129-1131.