Nonsteroidal aromatase inhibitors for the treatment of breast cancer: An update

Anti-Cancer Agents in Medicinal Chemistry

Volumn 14, Issue 1, 2014, Pages 54-65

  Gobbi, Silvia ^a   Rampa, Angela ^a   Belluti, Federica ^a   Bisi, Alessandra ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

Anticancer; Aromatase inhibitors; Breast cancer; Chemopreventive; CYP19; Cytochrome P450; Drug discovery; Endocrine therapy; Estrogens; Flavonoids; Natural products; Nonsteroidal

Indexed keywords

4 [N (4 BROMOBENZYL) N (1,2,4 TRIAZOL 4 YL)AMINO]BENZONITRILE; AMINOGLUTETHIMIDE; ANASTROZOLE; APIGENIN; AROMATASE INHIBITOR; BIOCHANIN A; CHRYSIN; CYTOCHROME P450; CYTOCHROME P450 17; ESTROGEN; EXEMESTANE; FADROZOLE; FORMESTANE; GENISTEIN; HESPERETIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; IROSUSTAT; ISOFLAVONOID; LETROZOLE; LUTEOLIN; NARINGENIN; NONSTEROIDAL AROMATASE INHIBITOR; PINOCEMBRINE; PROSTAGLANDIN E2; RESVERATROL; TAMOXIFEN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VOROZOLE; XENOBIOTIC AGENT;

BINDING SITE; BREAST CANCER; CANCER RECURRENCE; CHEMOPROPHYLAXIS; CLINICAL TRIAL; CRYSTAL STRUCTURE; CYTOTOXICITY; DISEASE COURSE; ENZYME SUBSTRATE COMPLEX; HUMAN; MOLECULAR DOCKING; OVERALL SURVIVAL; REVIEW; STRUCTURE ACTIVITY RELATION; TUMOR GROWTH;

ANTICARCINOGENIC AGENTS; ANTINEOPLASTIC AGENTS; AROMATASE; AROMATASE INHIBITORS; BREAST NEOPLASMS; DRUG DESIGN; DRUG RESISTANCE, NEOPLASM; ESTROGEN RECEPTOR MODULATORS; FEMALE; FLAVONOIDS; HUMANS; STERYL-SULFATASE; STRUCTURE-ACTIVITY RELATIONSHIP; TAMOXIFEN;

EID: 84899418068     PISSN: 18715206     EISSN: 18755992     Source Type: Journal    
DOI: 10.2174/18715206113139990306     Document Type: Review

References (99)

1. Jemal, A.; Siegel, R.; Ward, E.; Murray, T.; Xu, J.; Smigal, C.; Thun, M.J. Cancer statistics, 2006. CA Cancer. J. Clin., 2006, 56(2), 106-130.
2. Dahlman-Wright, K.; Cavailles, V.; Fuqua, S.A.; Jordan, V.C.; Katzenellenbogen, J.A.; Korach, K.S.; Maggi, A.; Muramatsu, M.; Parker, M.G.; Gustafsson, J.A. International Union of Pharmacology. LXIV. Estrogen receptors. Pharmacol. Rev., 2006, 58(4), 773-781.
3. Heldring, N.; Pike, A.; Andersson, S.; Matthews, J.; Cheng, G.; Hartman, J.; Tujague, M.; Strom, A.; Treuter, E.; Warner, M.; Gustafsson, J.A. Estrogen receptors: How do they signal and what are their targets. Physiol. Rev., 2007, 87(3), 905-931.
4. Simpson, E.R. Sources of estrogen and their importance. J. Steroid. Biochem. Mol. Biol., 2003, 86(3-5), 225-230.
5. Kulendran, M.; Salhab, M.; Mokbel, K. Oestrogen-synthesising enzymes and breast cancer. Anticancer Res., 2009, 29(4), 1095-1109.
6. Wang, T.; You, Q.; Huang, F.S.; Xiang, H. Recent advances in selective estrogen receptor modulators for breast cancer. Mini. Rev. Med. Chem., 2009, 9(10), 1191-1201.
7. Puhalla, S.; Brufsky, A.; Davidson, N. Adjuvant endocrine therapy for premenopausal women with breast cancer. Breast, 2009, 18(Suppl 3), S122-S130.
8. Larionov, A.A.; Miller, W.R. Challenges in defining predictive markers for response to endocrine therapy in breast cancer. Future Oncol., 2009, 5(9), 1415-1428.
9. Dowsett, M.; Haynes, B.P. Hormonal effects of aromatase inhibitors: Focus on premenopausal effects and interaction with tamoxifen. J. Steroid. Biochem. Mol. Biol., 2003, 86(3-5), 255-263.
10. Smith, I.E. Aromatase inhibitors--extending the benefits of adjuvant therapy beyond tamoxifen. Breast, 2004, 13(Suppl 1), S3-S9.
11. Altundag, K.; Ibrahim, N.K. Aromatase inhibitors in breast cancer: An overview. Oncologist, 2006, 11(6), 553-562.
12. Chumsri, S.; Howes, T.; Bao, T.; Sabnis, G.; Brodie, A. Aromatase, aromatase inhibitors, and breast cancer. J. Steroid. Biochem. Mol. Biol., 2011, 125(1-2), 13-22.
13. Reed, M.J.; Purohit, A.; Woo, L.W.; Newman, S.P.; Potter, B.V. Steroid sulfatase: Molecular biology, regulation, and inhibition. Endocr. Rev., 2005, 26(2), 171-202.
14. Brodie, A.M.; Njar, V.C. Aromatase inhibitors in advanced breast cancer: Mechanism of action and clinical implications. J. Steroid. Biochem. Mol. Biol., 1998, 66(1-2), 1-10.
15. Recanatini, M.; Cavalli, A.; Valenti, P. Nonsteroidal aromatase inhibitors: Recent advances. Med. Res. Rev., 2002, 22(3), 282-304.
16. Ghosh, D.; Griswold, J.; Erman, M.; Pangborn, W. Structural basis for androgen specificity and oestrogen synthesis in human aromatase. Nature, 2009, 457(7226), 219-223.
17. Ghosh, D.; Griswold, J.; Erman, M.; Pangborn, W. X-ray structure of human aromatase reveals an androgen-specific active site. J. Steroid. Biochem. Mol. Biol., 2010, 118(4-5), 197-202.
18. Miller, W.R.; Bartlett, J.; Brodie, A.M.; Brueggemeier, R.W.; Di Salle, E.; Lønning, P.E.; Llombart, A.; Maass, N.; Maudelonde, T.; Sasano, H.; Goss, P.E. Aromatase inhibitors: Are there differences between steroidal and nonsteroidal aromatase inhibitors and do they matter? Oncologist, 2008, 13(8), 829-837.
19. Deeks, E.D.; Scott, L.J. Exemestane: A review of its use in postmenopausal women with breast cancer. Drugs, 2009, 69(7), 889-918.
20. Gobbi, S.; Cavalli, A.; Bisi, A.; Recanatini, M. From nonsteroidal aromatase inhibitors to multifunctional drug candidates: Classic and innovative strategies for the treatment of breast cancer. Curr. Top. Med. Chem., 2008, 8(10), 869-887.
21. Barnadas, A.; Estévez, L.G.; Lluch-Hernández, A.; Rodriguez-Lescure, A.; Rodriguez-Sanchez, C.; Sanchez-Rovira, P. An overview of letrozole in postmenopausal women with hormone-responsive breast cancer. Adv. Ther., 2011, 28(12), 1045-1058.
22. Kelly, C.M.; Buzdar, A.U. Anastrozole. Exp. Opin. Drug Saf., 2010, 9(6), 995-1003.
23. Lumachi, F.; Luisetto, G.; Basso, S.M.; Basso, U.; Brunello, A.; Camozzi, V. Endocrine therapy of breast cancer. Curr. Med. Chem., 2011, 18(4), 513-522.
24. Regan, M.M.; Price, K.N.; Giobbie-Hurder, A.; Thürlimann, B.; Gelber, R.D.; Group, I.B.C.S.G.A.B.-C. Interpreting Breast International Group(BIG) 1-98: A randomized, double-blind, phase III trial comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive, early breast cancer. Breast Cancer. Res., 2011, 13(3), 209.
25. Burstein, H.J.; Prestrud, A.A.; Seidenfeld, J.; Anderson, H.; Buchholz, T.A.; Davidson, N.E.; Gelmon, K.E.; Giordano, S.H.; Hudis, C.A.; Malin, J.; Mamounas, E.P.; Rowden, D.; Solky, A.J.; Sowers, M.R.; Stearns, V.; Winer, E.P.; Somerfield, M.R.; Griggs, J.J.; Oncology, A.S.O.C. American Society of Clinical Oncology clinical practice guideline: Update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J. Clin. Oncol., 2010, 28(23), 3784-3796.
26. Goldhirsch, A.; Ingle, J.N.; Gelber, R.D.; Coates, A.S.; Thürlimann, B.; Senn, H.J.; members, P. Thresholds for therapies: Highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann. Oncol., 2009, 20(8), 1319-1329.
27. Forbes, J.F.; Cuzick, J.; Buzdar, A.; Howell, A.; Tobias, J.S.; Baum, M. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol., 2008, 9(1), 45-53.
28. Cuzick, J.; Sestak, I.; Baum, M.; Buzdar, A.; Howell, A.; Dowsett, M.; Forbes, J.F. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol., 2010, 11(12), 1135-1141.
29. Mouridsen, H.; Giobbie-Hurder, A.; Goldhirsch, A.; Thürlimann, B.; Paridaens, R.; Smith, I.; Mauriac, L.; Forbes, J.F.; Zrice, K.N.; Regan, M.M.; Gelber, R.D.; Coates, A.S.; Group, B.-C. Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. N. Engl. J. Med., 2009, 361(8), 766-776.
30. Colleoni, M.; Giobbie-Hurder, A.; Regan, M.M.; Thürlimann, B.; Mouridsen, H.; Mauriac, L.; Forbes, J.F.; Paridaens, R.; Láng, I.; Smith, I.; Chirgwin, J.; Pienkowski, T.; Wardley, A.; Price, K.N.; Gelber, R.D.; Coates, A.S.; Goldhirsch, A. Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study. J. Clin. Oncol., 2011, 29(9), 1117-1124.
31. Dowsett, M.; Cuzick, J.; Ingle, J.; Coates, A.; Forbes, J.; Bliss, J.; Buyse, M.; Baum, M.; Buzdar, A.; Colleoni, M.; Coombes, C.; Snowdon, C.; Gnant, M.; Jakesz, R.; Kaufmann, M.; Boccardo, F.; Godwin, J.; Davies, C.; Peto, R. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J. Clin. Oncol., 2010, 28(3), 509-518.
32. Dent, S.F.; Gaspo, R.; Kissner, M.; Pritchard, K.I. Aromatase inhibitor therapy: Toxicities and management strategies in the treatment of postmenopausal women with hormone-sensitive early breast cancer. Breast Cancer Res. Treat., 2011, 126(2), 295-310.
33. Gaillard, S.; Stearns, V. Aromatase inhibitor-associated bone and musculoskeletal effects: New evidence defining etiology and strategies for management. Breast Cancer Res., 2011, 13(2), 205.
34. Beresford, M.; Tumur, I.; Chakrabarti, J.; Barden, J.; Rao, N.; Makris, A. A qualitative systematic review of the evidence base for non-cross-resistance between steroidal and non-steroidal aromatase inhibitors in metastatic breast cancer. Clin. Oncol.(R. Coll. Radiol.), 2011, 23(3), 209-215.
35. Miller, W.R.; Larionov, A.A. Understanding the mechanisms of aromatase inhibitor resistance. Breast Cancer Res., 2012, 14(1), 201.
36. Banting, L.; Ahmed, S. Aromatase: The enzyme and its inhibition. Anticancer Agents Med. Chem., 2009, 9(6), 627-641.
37. Jiao, J.; Xiang, H.; Liao, Q. Recent advancement in nonsteroidal aromatase inhibitors for treatment of estrogen-dependent breast cancer. Curr. Med. Chem., 2010, 17(30), 3476-3487.
38. Lézé, M.P.; Palusczak, A.; Hartmann, R.W.; Le Borgne, M. Synthesis of 6- or 4-functionalized indoles via a reductive cyclization approach and evaluation as aromatase inhibitors. Bioorg. Med. Chem. Lett., 2008, 18(16), 4713-4715.
39. Leze, M.P.; Le Borgne, M.; Marchand, P.; Loquet, D.; Kogler, M.; Le Baut, G.; Palusczak, A.; Hartmann, R.W. 2- and 3-[(aryl)(azolyl)methyl]indoles as potential non-steroidal aromatase inhibitors. J. Enzyme Inhib. Med. Chem., 2004, 19(6), 549-557.
40. Le Borgne, M.; Marchand, P.; Nourrisson, M.R.; Loquet, D.; Palzer, M.; Le Baut, G.; Hartmann, R.W. Synthesis and biological evaluation of 3-(azolylmethyl)-1H-indoles and 3-(alpha-azolylbenzyl)-1H-indoles as selective aromatase inhibitors. J. Enzyme Inhib. Med. Chem., 2007, 22(5), 667-676.
41. Leze, M.P.; Le Borgne, M.; Pinson, P.; Palusczak, A.; Duflos, M.; Le Baut, G.; Hartmann, R.W. Synthesis and biological evaluation of 5-[(aryl)(1H-imidazol-1-yl)methyl]-1H-indoles: Potent and selective aromatase inhibitors. Bioorg. Med. Chem. Lett, 2006, 16(5), 1134-1137.
42. Doiron, J.; Soultan, A.H.; Richard, R.; Touré, M.M.; Picot, N.; Cuperlovic-Culf, M.; Robichaud, G.A.; Touaibia, M. Synthesis and structure-activity relationship of 1- and 2-substituted-1,2,3-triazole letrozole-based analogues as aromatase inhibitors. Eur. J. Med. Chem., 2011, 46(9), 4010-4024.
43. Gobbi, S.; Zimmer, C; Belluti, F.; Rampa, A.; Hartmann, R.W.; Recanatini, M.; Bisi, A. Novel highly potent and selective nonsteroidal aromatase inhibitors: Synthesis, biological evaluation and structure-activity relationships investigation. J. Med. Chem., 2010, 53(14), 5347-5351.
44. Recanatini, M.; Bisi, A.; Cavalli, A.; Belluti, F.; Gobbi, S.; Rampa, A.; Valenti, P.; Palzer, M.; Palusczak, A.; Hartmann, RW. A new class of nonsteroidal aromatase inhibitors: Design and synthesis of chromone and xanthone derivatives and inhibition of the P450 enzymes aromatase and 17 alpha-hydroxylase/C17,20-lyase. J. Med. Chem., 2001, 44(5), 672-680.
45. Yahiaoui, S.; Pouget, C; Buxeraud, J.; Chulia, A.J.; Fagnère, C. Lead optimization of 4-imidazolylflavans: New promising aromatase inhibitors. Eur. J. Med. Chem., 2011, 46(6), 2541-2545.
46. Yahiaoui, S.; Fagnere, C; Pouget, C; Buxeraud, J.; Chulia, A.J. New 7,8-benzoflavanones as potent aromatase inhibitors: Synthesis and biological evaluation. Bioorg. Med. Chem., 2008, 16(3), 1474-1480.
47. Pouget, C; Fagnere, C; Basly, J.P.; Habrioux, G.; Chulia, A.J. Design, synthesis and evaluation of 4-imidazolylflavans as new leads for aromatase inhibition. Bioorg. Med. Chem. Lett, 2002, 12(20), 2859-2861.
48. Leonetti, F.; Favia, A.; Rao, A.; Aliano, R.; Paluszcak, A.; Hartmann, R.W.; Carotti, A. Design, synthesis, and 3D QSAR of novel potent and selective aromatase inhibitors. J. Med. Chem., 2004, 47(27), 6792-6803.
49. Stefanachi, A.; Favia, A.D.; Nicolotti, O.; Leonetti, F.; Pisani, L.; Catto, M.; Zimmer, C; Hartmann, R.W.; Carotti, A. Design, synthesis, and biological evaluation of imidazolyl derivatives of 4,7-disubstituted coumarins as aromatase inhibitors selective over 17-a-hydroxylase/ C17-20 lyase. J. Med. Chem., 2011, 54(6), 1613-1625.
50. McNulty, J.; Nair, J.J.; Vurgun, N.; Difrancesco, B.R.; Brown, C.E.; Tsoi, B.; Crankshaw, D.J.; Holloway, A.C. Discovery of a novel class of aldol-derived 1,2,3-triazoles: Potent and selective inhibitors of human cytochrome P450 19A1(aromatase). Bioorg. Med. Chem. Lett, 2012, 22(1), 718-722.
51. Nakajin, S.; Shinoda, M.; Hall, P.F. Purification to homogeneity of aromatase from human placenta. Biochem. Biophys. Res. Commun., 1986, 134(2), 704-710.
52. Kellis, J.T.; Vickery, L.E. Purification and characterization of human placental aromatase cytochrome P-450. J. Biol. Chem., 1987, 262(9), 4413-4420.
53. Amarneh, B.; Simpson, E.R. Expression of a recombinant derivative of human aromatase P450 in insect cells utilizing the baculovirus vector system. Mol. Cell. Endocrinol, 1995, 109(2), R1-5.
54. Hong, Y.; Cho, M.; Yuan, Y.C.; Chen, S. Molecular basis for the interaction of four different classes of substrates and inhibitors with human aromatase. Biochem. Pharmacol, 2008, 75(5), 1161-1169.
55. Castellano, S.; Stefancich, G.; Ragno, R.; Schewe, K.; Santoriello, M.; Caroli, A; Hartmann, R.W.; Sbardella, G. CYP19 (aromatase): Exploring the scaffold flexibility for novel selective inhibitors. Bioorg. Med. Chem., 2008, 16(18), 8349-8358.
56. Favia, A.D.; Cavalli, A.; Masetti, M.; Carotti, A.; Recanatini, M. Three-dimensional model of the human aromatase enzyme and density functional parameterization of the iron-containing protoporphyrin IX for a molecular dynamics study of heme-cysteinato cytochromes. Proteins, 2006, 62(4), 1074-1087.
57. Jain, A.N. Surflex: Fully automatic flexible molecular docking using a molecular similarity-based search engine. J. Med. Chem., 2003, 46(4), 499-511.
58. Ragno, R.; Simeoni, S.; Valente, S.; Massa, S.; Mai, A. 3-D QSAR studies on histone deacetylase inhibitors. A GOLPE/GRID approach on different series of compounds. J. Chem. Inf. Model, 2006, 46(3), 1420-1430.
59. Neves, M.A.; Dinis, T.C.; Colombo, G.; Sá e Melo, M.L. Fast three dimensional pharmacophore virtual screening of new potent non-steroid aromatase inhibitors. J. Med. Chem., 2009, 52(1), 143-150.
60. Caporuscio, F.; Rastelli, G.; Imbriano, C.; Del Rio, A. Structure-based design of potent aromatase inhibitors by high-throughput docking. J. Med. Chem., 2011, 54(12), 4006-4017.
61. Narayana, B.L.; Kishore, D.P.; Balakumar, C.; Rao, K.V.; Kaur, R.; Rao, A.R.; Murthy, J.N.; Ravikumar, M. Molecular modeling evaluation of non-steroidal aromatase inhibitors. Chem. Biol. Drug Des., 2012, 79(5), 674-682.
62. Gobbi, S.; Cavalli, A.; Rampa, A.; Belluti, F.; Piazzi, L.; Paluszcak, A.; Hartmann, R.W.; Recanatini, M.; Bisi, A. Lead optimization providing a series of flavone derivatives as potent nonsteroidal inhibitors of the cytochrome P450 aromatase enzyme. J. Med. Chem., 2006, 49(15), 4777-4780.
63. Pouget, C.; Fagnere, C.; Basly, J.P.; Besson, A.E.; Champavier, Y.; Habrioux, G.; Chulia, A.J. Synthesis and aromatase inhibitory activity of flavanones. Pharm. Res., 2002, 19(3), 286-291.
64. Cavalli, A.; Bisi, A.; Bertucci, C.; Rosini, C.; Paluszcak, A.; Gobbi, S.; Giorgio, E.; Rampa, A.; Belluti, F.; Piazzi, L.; Valenti, P.; Hartmann, R.W.; Recanatini, M. Enantioselective nonsteroidal aromatase inhibitors identified through a multidisciplinary medicinal chemistry approach. J. Med. Chem., 2005, 48(23), 7282-7289.
65. Bonfield, K.; Amato, E.; Bankemper, T.; Agard, H.; Steller, J.; Keeler, J.M.; Roy, D.; McCallum, A.; Paula, S.; Ma, L. Development of a new class of aromatase inhibitors: Design, synthesis and inhibitory activity of 3-phenylchroman-4-one (isoflavanone) derivatives. Bioorg. Med. Chem., 2012, 20(8), 2603-2613.
66. Balunas, M.J.; Su, B.; Brueggemeier, R.W.; Kinghorn, A.D. Natural products as aromatase inhibitors. Anticancer Agents Med. Chem., 2008, 8(6), 646-682.
67. Balunas, M.J.; Kinghorn, A.D. Natural compounds with aromatase inhibitory activity: An update. Planta Med., 2010, 76(11), 1087-1093.
68. Bajgai, S.P.; Prachyawarakorn, V.; Mahidol, C.; Ruchirawat, S.; Kittakoop, P. Hybrid flavan-chalcones, aromatase and lipoxygenase inhibitors, from Desmos cochinchinensis. Phytochemistry, 2011, 72(16), 2062-2067.
69. Nelson, M.A. Inhibition of lipoxygenase activity: Implications for the treatment and chemoprevention of prostate cancer. Cancer Biol. Ther., 2007, 6(2), 237.
70. Rice, L.W. Hormone prevention strategies for breast, endometrial and ovarian cancers. Gynecol. Oncol., 2010, 118(2), 202-207.
71. Bulun, S.E.; Lin, Z.; Zhao, H.; Lu, M.; Amin, S.; Reierstad, S.; Chen, D. Regulation of aromatase expression in breast cancer tissue. Ann. N Y. Acad. Sci., 2009, 1155, 121-131.
72. Wang, Y.; Man Gho, W.; Chan, F.L.; Chen, S.; Leung, L.K. The red clover (Trifolium pratense) isoflavone biochanin A inhibits aromatase activity and expression. Br. J. Nutr., 2008, 99(2), 303-310.
73. Zhou, D.; Zhou, C.; Chen, S. Gene regulation studies of aromatase expression in breast cancer and adipose stromal cells. J. Steroid. Biochem. Mol. Biol., 1997, 61(3-6), 273-280.
74. Li, F.; Ye, L.; Lin, S.M.; Leung, L.K. Dietary flavones and flavonones display differential effects on aromatase (CYP19) transcription in the breast cancer cells MCF-7. Mol. Cell. Endocrinol., 2011, 344(1-2), 51-58.
75. Howell, A. The endocrine prevention of breast cancer. Best Pract. Res. Clin. Endocrinol. Metab., 2008, 22(4), 615-623.
76. Aggarwal, B.B.; Gehlot, P. Inflammation and cancer: How friendly is the relationship for cancer patients? Curr. Opin. Pharmacol., 2009, 9(4), 351-369.
77. Aktan, F. iNOS-mediated nitric oxide production and its regulation. Life Sci., 2004, 75(6), 639-653.
78. Escárcega, R.O.; Fuentes-Alexandro, S.; García-Carrasco, M.; Gatica, A.; Zamora, A. The transcription factor nuclear factor-kappa B and cancer. Clin. Oncol.(R. Coll. Radiol.), 2007, 19(2), 154-161.
79. Ross, D.; Kepa, J.K.; Winski, S.L.; Beall, H.D.; Anwar, A.; Siegel, D. NAD(P)H: Quinone oxidoreductase 1(NQO1): Chemoprotection, bioactivation, gene regulation and genetic polymorphisms. Chem. Biol. Interact., 2000, 129(1-2), 77-97.
80. Celli, C.M.; Tran, N.; Knox, R.; Jaiswal, A.K. NRH: Quinone oxidoreductase 2(NQO2) catalyzes metabolic activation of quinones and anti-tumor drugs. Biochem. Pharmacol., 2006, 72(3), 366-376.
81. Maiti, A.; Cuendet, M.; Croy, V.L.; Endringer, D.C.; Pezzuto, J.M.; Cushman, M. Synthesis and biological evaluation of (+/-)-abyssinone II and its analogues as aromatase inhibitors for chemoprevention of breast cancer. J. Med. Chem., 2007, 50(12), 2799-2806.
82. Maiti, A.; Reddy, P.V.; Sturdy, M.; Marler, L.; Pegan, S.D.; Mesecar, A.D.; Pezzuto, J.M.; Cushman, M. Synthesis of casimiroin and optimization of its quinone reductase 2 and aromatase inhibitory activities. J. Med. Chem., 2009, 52(7), 1873-1884.
83. Baur, J.A.; Sinclair, D.A. Therapeutic potential of resveratrol: The in vivo evidence. Nat. Rev. Drug Discov., 2006, 5(6), 493-506.
84. Sun, B.; Hoshino, J.; Jermihov, K.; Marler, L.; Pezzuto, J.M.; Mesecar, A.D.; Cushman, M. Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer. Bioorg. Med. Chem., 2010, 18(14), 5352-5366.
85. Mayhoub, A.S.; Marler, L.; Kondratyuk, T.P.; Park, E.J.; Pezzuto, J.M.; Cushman, M. Optimizing thiadiazole analogues of resveratrol versus three chemopreventive targets. Bioorg. Med. Chem., 2012, 20(1), 510-520.
86. Mayhoub, A.S.; Marler, L.; Kondratyuk, T.P.; Park, E.J.; Pezzuto, J.M.; Cushman, M. Optimization of the aromatase inhibitory activities of pyridylthiazole analogues of resveratrol. Bioorg. Med. Chem., 2012, 20(7), 2427-2434.
87. Howarth, N.M.; Purohit, A.; Reed, M.J.; Potter, B.V. Estrone sulfamates: Potent inhibitors of estrone sulfatase with therapeutic potential. J. Med. Chem., 1994, 37(2), 219-221.
88. Woo, L.W.; Purohit, A.; Potter, B.V. Development of steroid sulfatase inhibitors. Mol. Cell. Endocrinol., 2011, 340(2), 175-185.
89. Morphy, R.; Rankovic, Z. Designed multiple ligands. An emerging drug discovery paradigm. J. Med. Chem., 2005, 48(21), 6523-6543.
90. Woo, L.W.; Sutcliffe, O.B.; Bubert, C.; Grasso, A.; Chander, S.K.; Purohit, A.; Reed, M.J.; Potter, B.V. First dual aromatase-steroid sulfatase inhibitors. J. Med. Chem., 2003, 46(15), 3193-3196.
91. Woo, L.W.; Bubert, C.; Sutcliffe, O.B.; Smith, A.; Chander, S.K.; Mahon, M.F.; Purohit, A.; Reed, M.J.; Potter, B.V. Dual aromatase-steroid sulfatase inhibitors. J. Med. Chem., 2007, 50(15), 3540-3560.
92. Wood, P.M.; Woo, L.W.; Labrosse, J.R.; Trusselle, M.N.; Abbate, S.; Longhi, G.; Castiglioni, E.; Lebon, F.; Purohit, A.; Reed, M.J.; Potter, B.V. Chiral aromatase and dual aromatase-steroid sulfatase inhibitors from the letrozole template: Synthesis, absolute configuration, and in vitro activity. J. Med. Chem., 2008, 51(14), 4226-4238.
93. Jackson, T.; Woo, L.W.; Trusselle, M.N.; Chander, S.K.; Purohit, A.; Reed, M.J.; Potter, B.V. Dual aromatase-sulfatase inhibitors based on the anastrozole template: Synthesis, in vitro SAR, molecular modelling and in vivo activity. Org. Biomol. Chem., 2007, 5(20), 2940-2952.
94. Woo, L.W.; Jackson, T.; Putey, A.; Cozier, G.; Leonard, P.; Acharya, K.R.; Chander, S.K.; Purohit, A.; Reed, M.J.; Potter, B.V. Highly potent first examples of dual aromatase-steroid sulfatase inhibitors based on a biphenyl template. J. Med. Chem., 2010, 53(5), 2155-2170.
95. Wood, P.M.; Woo, L.W.; Thomas, M.P.; Mahon, M.F.; Purohit, A.; Potter, B.V. Aromatase and dual aromatase-steroid sulfatase inhibitors from the letrozole and vorozole templates. ChemMedChem, 2011, 6(8), 1423-1438.
96. Furet, P.; Batzl, C.; Bhatnagar, A.; Francotte, E.; Rihs, G.; Lang, M. Aromatase inhibitors: Synthesis, biological activity, and binding mode of azole-type compounds. J. Med. Chem., 1993, 36(10), 1393-1400.
97. Vanden Bossche, H.; Willemsens, G.; Roels, I.; Bellens, D.; Moereels, H.; Coene, M.C.; Le Jeune, L.; Lauwers, W.; Janssen, P.A. R 76713 and enantiomers: Selective, nonsteroidal inhibitors of the cytochrome P450-dependent oestrogen synthesis. Biochem. Pharmacol., 1990, 40(8), 1707-1718.
98. Wang, M.; Mickens, J.; Gao, M.; Miller, K.D.; Sledge, G.W.; Hutchins, G.D.; Zheng, Q.H. Design and synthesis of carbon-11-labeled dual aromatase-steroid sulfatase inhibitors as new potential PET agents for imaging of aromatase and steroid sulfatase expression in breast cancer. Steroids, 2009, 74(12), 896-905.
99. Colleoni, M.; Giobbie-Hurder, A. Benefits and adverse effects of endocrine therapy. Ann. Oncol., 2010, 21(Suppl 7), vii107- vii111.