Libraries of 2β-(N-substituted piperazino)-5α-androstane- 3α, 17β-diols: Chemical synthesis and cytotoxic effects on human leukemia HL-60 cells and on normal lymphocytes

Molecular Diversity

Volumn 15, Issue 2, 2011, Pages 317-339

  Roy, Jenny ^a,b   Maltais, René ^a,b   Jegham, Hajer ^a,b   Poirier, Donald ^a,b  

^a LAVAL UNIVERSITY   (Canada)

^b UNIVERSITÉ LAVAL   (Canada)

Author keywords

Aminosteroid; Androstane; Cancer; HL 60 cells; Solid phase synthesis

Indexed keywords

1 [ 2 [ 4 [(2BETA, 3ALPHA, 5ALPHA, 17BETA) 3,17 DIHYDROXYANDROSTAN 2 YL]PIPERAZIN 1 YL]CARBONYL]PYRROLIDIN 1 YL] 3 PHENYLPROP 2 EN 1 ONE; 3 ACETYL N [ 1 [4 [(2BETA, 3ALPHA, 5ALPHA, 17BETA) 3,17 DIHYDROXYANDROSTAN 2 YL]PIPERAZIN 1 YL] 1 OXO 3 PHENYLPROPAN 2 YL]BENZAMIDE; 4 [[ 2 [[ 4 [(2BETA, 3ALPHA, 5ALPHA, 17BETA) 3,17 DIHYDROXYANDROSTAN 2 YL]PIPERAZIN 1 YL]CARBONYL]PYRROLIDIN 1 YL]CARBONYL]BENZONITRILE; [4 [(2BETA, 3ALPHA, 5ALPHA, 17BETA) 3,17 DIHYDROXYANDROSTAN 2 YL]PIPERAZIN 1 YL] 1 [[4 (PROP 1 EN 2YL)CYCLOHEX 1 EN 1 YL]CARBONYL]PYRROLIDIN 2 YL]METHANONE; [4 [(2BETA, 3ALPHA, 5ALPHA, 17BETA) 3,17 DIHYDROXYANDROSTAN 2 YL]PIPERAZIN 1 YL] [1 (NAPHTALEN 1 YLCARBONYL)PYRROLIDIN 2 YL]METHANONE; [4 [(2BETA,3ALPHA,5ALPHA,17BETA) 3,17 DIHYDROXYANDROSTAN 2 YL]PIPERAZIN 1 YL] [ 2 [(2 METHYLCYCLOPROPYL)CARBONYL] 1,2,3,4 TETRAHYDROISOQUINOLIN 3 YL]METHANONE; ANTINEOPLASTIC AGENT; DOXORUBICIN; STEROID; UNCLASSIFIED DRUG; ANDROSTANEDIOL; DRUG DERIVATIVE;

ARTICLE; CANCER INHIBITION; CYTOTOXICITY; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; HYDROPHOBICITY; IC 50; LEUKEMIA CELL; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION; CELL PROLIFERATION; CELL STRAIN HL 60; CELL SURVIVAL; CHEMISTRY; DRUG EFFECT; LYMPHOCYTE; MOLECULAR LIBRARY; SYNTHESIS;

ANDROSTANE-3,17-DIOL; CELL PROLIFERATION; CELL SURVIVAL; HL-60 CELLS; HUMANS; LYMPHOCYTES; SMALL MOLECULE LIBRARIES;

EID: 80051573783     PISSN: 13811991     EISSN: 1573501X     Source Type: Journal    
DOI: 10.1007/s11030-010-9273-2     Document Type: Article

References (24)

1. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Fewer EJ, Thun MJ (2005) Cancer statistic 2005. Cancer J Clin 55:10-30. doi:10.3322/canjclin. 55.1.10
2. He Q, Jiang D (1999) A novel aminosteroid is active for proliferation inhibition and differentiation induction of human acute myeloid leukemia HL-60 cells. Leuk Res 23:369-372. doi:10.1016/S0145-2126 (98) 00160-X (Pubitemid 29166771)
3. Thibeault D, Poirier D (2003) An efficient method for the regioselective aminolysis of 2, 3α-steroidal epoxide. Synlett 8:1192-1194. doi:10.1055/s-2003-39901 (Pubitemid 36793710)
4. Thibeault D, Roy J, DeRoy P, Poirier D (2008) Chemical synthesis of 2β-amino-5α-androstane-3α, 17β-diols and biological evaluation of their antiproliferative effect on HL-60 acute myeloid leukemia cells. Bioorg Med Chem 16:5062-5077. doi:10.1016/j.bmc. 2008.03.031 (Pubitemid 351625881)
5. Maltais R, Tremblay MR, Poirier D (2000) Solid phase synthesis of hydroxysteroids using the diethylsilyloxy linker. J Comb Chem 2:604-614. doi:10.1021/cc0000242
6. Maltais R, Luu-The V, Poirier D (2001) Parallel solid-phase synthesis of 3β-peptido-3α-hydroxy-5α-androstan-17-one derivatives for inhibition of type 3 17β-hydroxysteroid dehydrogenase. Bioorg Med Chem 9:3101-3111. doi:10.1016/S0968-0896 (01) 00182-1 (Pubitemid 33065610)
7. Ciobanu LC, Poirier D (2003) Solid-phase syntesis of 17α-substitued estradiol sulfamate and phenol libraries using the multidetachable sulfamate linker. J Comb Chem 5:429-440. doi:10.1021/cc020115u (Pubitemid 37140554)
8. Maltais R, Mercier C, Labrie F, Poirier D (2005) Solid-phase synthesis of model libraries of 3α, 17β-dihydroxy-16α-aminoethyl-N- substitued)-5α-androstanes for the development of steroidal therapeutic agents. Mol Divers 9:67-79. doi:10.1007/s11030-005-1312-z (Pubitemid 40394841)
9. Maltais R, Tremblay MR, Ciobanu LC, Poirier D (2004) Steroids and combinatorial chemistry. J Comb Chem 6:443-456. doi:10. 1021/cc030118m (Pubitemid 39091263)
10. Poirier D, Maltais R (2006) Solid-phase organic synthesis (SPOS) of modulators of estrogenic and androgenic action. Mini Rev Med Chem 6:37-52. doi:10.2174/138955706775197802
11. Ciobanu LC, Poirier D (2006) Synthesis of libraries of 16β-aminopropyl estradiol derivatives for targeting two key steroidogenic enzymes. ChemMedChem 1:1249-1259. doi:10.1002/cmdc. 200600071 (Pubitemid 44786931)
12. Roy J, DeRoy P, Poirier D (2007) Development of aminosteroids with cytotoxic effect against leukemia using parallel solid-phase approach. J Comb Chem 9:347-358. doi:10.1021/cc060098z
13. Roy J (2006) Synthèse chimique et activité biologique d'agents stéroïdiens pour le traitement du cancer de la prostate et de la leucémie. PhD thesis, Laval University (Québec, Canada), Chap. 4, pp 194-216. http://ariane.ulaval.ca/cgi-bin/recherche.cgi?qu=a1595498
14. Robak T, Wierzbowska A (2009) Current and emerging therapies for acute myeloid leukemia. Clin Ther 31:2349-2370. doi:10.1016/j.clinthera.2009.11.017
15. A receptors. J Med Chem 40:1668-1681. doi:10.1021/jm960733n (Pubitemid 27231469)
16. Hudlicky M (1988) Fluorination with diethylaminosulfur trifluoride and related aminofluorosulfuranes. Org React 35:513-641. doi:10.1002/0471264180. or035.03
17. Decreau RA, Marson CM (2004) Synth Commun 34:4369-4385. doi:10.1081/SCC-200039449 (Pubitemid 39657525)
18. Bird TG, Fredericks PM, Jones ERH, Meakins GD (1979) Convenient general preparation of oxy-generated monofluoro-5α-androstanes using diethylaminosulfur trifluoride. J Chem Soc Chem Commun, 65-66. doi:10.1039/C39790000065
19. Druker BJ, Lydon NB (2000) Lessons learned from the development of an Abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J Clin Invest 105:3-7. doi:10.1172/JCI9083 (Pubitemid 30036380)
20. Fausel C (2007) Targeted chronic myeloid leukemia therapy: Seeking a cure. Am J Health Syst Pharm 64:S9-S15. doi:10.2146/ajhp070482 (Pubitemid 350276283)
21. Iriarte J, Rosenkranz G, Sondheimer F (1955) A synthesis of androsterone. J Org Chem 20:542-545. doi:10.1021/jo01122a018
22. Kagialis-Girard S, Mialou V, Chebel A, Chien WW, Tigaud I, Mokdad F, Badiou C, French MF (2007) Inhibition of normal lymphocyte proliferation by Indirubin-3'-monoxime: a multifactorial process. Leuk Lymphoma 48:605-615. doi:10.1080/10428190601059696 (Pubitemid 46487771)
23. Rocha DD, Gadelha Militao GC, Veras ML, Pessoa ODL, Rocha Silveira E, Negreiras Numes Alves AP, Odericode Moraes M, Pessoa C, Veras Costa-Lotufo L (2006) Selective cytotoxicity of withaphysalins in myeloid leukemia cell lines versus peripheral blood mononuclear cells. Life Sci 79:1692-1701. doi:10.1016/j. lfs.2006.05.026 (Pubitemid 44374548)
24. Cwynarski K, Laylor R, Macchiarulo E, Goldman J, Lombardi G, Melo JV, Dazzi F (2004) Imatinib inhibits the activation and proliferation of normal T lymphocytes in vitro. Leukemia 18:1332-1339. doi:10.1038/sj.leu.2403401 (Pubitemid 39136740)