Sterols as anticancer agents: Synthesis of ring-B oxygenated steroids, cytotoxic profile, and comprehensive SAR analysis

Journal of Medicinal Chemistry

Volumn 53, Issue 21, 2010, Pages 7632-7638

  Carvalho, João F S ^a   Silva, M Manuel Cruz ^a   Moreira, João N ^a,b   Simões, Sérgio ^a,b   Sá E Melo, M Luisa ^a  

^a UNIVERSITY OF COIMBRA   (Portugal)

^b UNIVERSITY OF COIMBRA   (Portugal)

Author keywords

[No Author keywords available]

Indexed keywords

3 BETA, 5 ALPHA, 6 BETA TRIHYDROXYSTEROID DERIVATIVE; 5 ALPHA, 6 ALPHA EPOXY 3 BETA HYDROXYCHOLESTAN 7 ONE; 6 BETA HEMIPHTHALATE; 7 BETA HYDROXYCHOLESTEROL; CHOLESTANE 3 BETA, 5 ALPHA, 6 BETA TRIOL; CISPLATIN; DOXORUBICIN; OXYSTEROL; OXYSTEROL 3 BETA YL HEMISUCCINATE DERIVATIVE; PHTHALIC ACID; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG SELECTIVITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; OXIDATION; OXYGENATION; STRUCTURE ACTIVITY RELATION;

ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CELL LINE; CELL LINE, TUMOR; CELL PROLIFERATION; CISPLATIN; DOXORUBICIN; DRUG SCREENING ASSAYS, ANTITUMOR; DRUG SYNERGISM; HUMANS; STEROLS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 78149265180     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm1007769     Document Type: Article

References (25)

1. Vejux, A.; Lizard, G. Cytotoxic effects of oxysterols associated with human diseases: induction of cell death (apoptosis and/or oncosis), oxidative and inflammatory activities, and phospholipidosis Mol. Aspects Med. 2009, 30, 153-170
2. Schroepfer, G. J. J. Oxysterols: modulators of cholesterol metabolism and other processes Physiol. Rev. 2000, 80, 361-554
3. Olkkonen, V. M.; Hynynen, R. Interactions of oxysterols with membranes and proteins Mol. Aspects Med. 2009, 30, 123-133
4. Pirillo, A.; Zhu, W.; Roma, P.; Galli, G.; Caruso, D.; Pellegatta, F.; Catapano, A. L. Oxysterols from oxidized LDL are cytotoxic but fail to induce hsp70 expression in endothelial cells FEBS Lett. 1999, 462, 113-116
5. Larsson, D. A.; Baird, S.; Nyhalah, J. D.; Yuan, X.-M.; Li, W. Oxysterol mixtures, in atheroma-relevant proportions, display synergistic and proapoptotic effects Free Radical Biol. Med. 2006, 41, 902-910
6. Biasi, F.; Leonarduzzi, G.; Vizio, B.; Zanetti, D.; Sevanian, A.; Sottero, B.; Verde, V.; Zingaro, B.; Chiarpotto, E.; Poli, G. Oxysterol mixtures prevent proapoptotic effects of 7-ketocholesterol in macrophages: implications for proatherogenic gene modulation FASEB J. 2004, 18, 693-695
7. Steffen, Y.; Wiswedel, I.; Peter, D.; Schewe, T.; Sies, H. Cytotoxicity of myeloperoxidase/nitrite-oxidized low-density lipoprotein toward endothelial cells is due to a high 7β-hydroxycholesterol to 7-ketocholesterol ratio Free Radical Biol. Med. 2006, 41, 1139-1150
8. Radhakrishnan, A.; Ikeda, Y.; Kwon, H.; Brown, M.; Goldstein, J. Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to Insig Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 6511-6518 (Pubitemid 47175533)
9. Ishimaru, C.; Yonezawa, Y.; Kuriyama, I.; Nishida, M.; Yoshida, H.; Mizushina, Y. Inhibitory effects of cholesterol derivatives on DNA polymerase and topoisomerase activities, and human cancer cell growth Lipids 2008, 43, 373-382
10. Fernández, C.; Lobo, M. d. V. T.; Gómez-Coronado, D.; Lasunción, M. A. Cholesterol is essential for mitosis progression and its deficiency induces polyploid cell formation Exp. Cell Res. 2004, 300, 109-120
11. Lemaire-Ewing, S.; Prunet, C.; Montange, T.; Vejux, A.; Berthier, A.; Bessède, G.; Corcos, L.; Gambert, P.; Néel, D.; Lizard, G. Comparison of the cytotoxic, pro-oxidant and pro-inflammatory characteristics of different oxysterols Cell Biol. Toxicol. 2005, 21, 97-114
12. Aiello, A.; Fattorusso, E.; Menna, M. Steroids from sponges: recent reports Steroids 1999, 64, 687-714
13. Wu, Q.; Huang, K. Protective effect of ebselen on cytotoxicity induced by cholestane-3β,5α,6β-triol in ECV-304 cells Biochim. Biophys. Acta 2006, 1761, 350-359
14. 5-steroids Tetrahedron 2010, 66, 2455-2462
15. Carvalho, J. F. S.; Silva, M. M. C.; Sá e Melo, M. L. Highly efficient epoxidation of unsaturated steroids using magnesium bis(monoperoxyphthalate) hexahydrate Tetrahedron 2009, 65, 2773-2781
16. Carvalho, J. F. S.; Silva, M. M. C.; Moreira, J. N.; Simões, S.; Sá e Melo, M. L. Efficient chemoenzymatic synthesis, cytotoxic evaluation and SAR of epoxysterols J. Med. Chem. 2009, 52, 4007-4019
17. Gerweck, L. E. The pH difference between tumor and normal tissue offers a tumor specific target for the treatment of cancer Drug Resist. Updates 2000, 3, 49-50
18. Massey, J. B.; Pownall, H. J. Structures of biologically active oxysterols determine their differential effects on phospholipid membranes Biochemistry 2006, 45, 10747-10758
19. Fretland, Adrian J.; Omiecinski, Curtis J. Epoxide hydrolases: biochemistry and molecular biology Chem.-Biol. Interact. 2000, 129, 41-59
20. Gerweck, L. E.; Vijayappa, S.; Kozin, S. Tumor pH controls the in vivo efficacy of weak acid and base chemotherapeutics Mol. Cancer Ther. 2006, 5, 1275-1279
21. Quílez, J.; García-Lorda, P.; Salas-Salvadó, J. Potential uses and benefits of phytosterols in diet: present situation and future directions Clin. Nutr. 2003, 22, 343-351
22. Ryan, E.; McCarthy, F. O.; Maguire, A. R.; O'Brien, N. M. Phytosterol oxidation products: their formation, occurrence, and biological effects Food Rev. Int. 2009, 25, 157-174
23. Roussi, S.; Winter, A.; Gosse, F.; Werner, D.; Zhang, X.; Marchioni, E.; Geoffroy, P.; Miesch, M.; Raul, F. Different apoptotic mechanisms are involved in the antiproliferative effects of 7β-hydroxysitosterol and 7β-hydroxycholesterol in human colon cancer cells Cell Death Differ. 2005, 12, 128-135
24. Hyun, J. W.; Holl, V.; Weltin, D.; Dufour, P.; Luu, B.; Bischoff, P. Effects of combinations of 7β-hydroxycholesterol and anticancer drugs or ionizing radiation on the proliferation of cultured tumor cells Anticancer Res. 2002, 22, 943-948
25. Li, W.; Johnson, H.; Yuan, X.-M.; Jonasson, L. 7β-Hydroxycholesterol induces natural killer cell death via oxidative lysosomal destabilization Free Radical Res. 2009, 43, 1072-1079