Login Register Cart 0
Generic placeholder image

Current Enzyme Inhibition

Editor-in-Chief

ISSN (Print): 1573-4080
ISSN (Online): 1875-6662

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Development of Steroidal Aromatase Inhibitors as Potential Anti-breast Cancer Agents

Author(s): Rahul B. Ghuge, Prashant R. Murumkar, Kailash M. Choudhary, Karan D. Joshi, Monica Chauhan, Rahul R. Barot and Mange R. Yadav*

Volume 16, Issue 1, 2020

Page: [45 - 62] Pages: 18

DOI: 10.2174/1573408016666200212094804

Price: $65

Abstract

Breast cancer is the most prevalent type of cancer and one of the leading causes of death among all the cancers affecting women worldwide. Preliminary cause of development of tumors in the breast cancer in post-menopausal women is mostly the increased estrogen levels in the body which could be the result of overexpression of aromatase CYP450 i.e. CYP19A1. Aromatase is the only enzyme present in humans that brings about aromatization of A-ring of 19-carbon androgens to form 18-carbon estrogens. Inhibiting aromatase enzyme thereby decreasing the estrogen levels in the postmenopausal women has been considered as an important strategy for the management of breast cancer. Three generations of aromatase inhibitors including steroidal viz. testolactone, formestane, exemestane and non-steroidal viz. aminoglutethimide, fadrozole, letrozole, anastrozole, the two classes of drugs have been approved for clinical use for the treatment of breast cancer. A large number of research and review articles have been reported so far describing the therapeutic efficacy of steroidal and non-steroidal aromatase inhibitors. However, steroidal aromatase inhibitors, being more selective inhibitors and having certain other advantages, overruled the discovery of novel aromatase inhibitors compared to the non-steroidal aromatase inhibitors which lack selectivity for CYP450 aromatase. In this review, efforts have been made to describe the developments of steroidal aromatase inhibitors to date.

Keywords: Androstenedione, aromatase inhibitors, breast cancer, CYP19A1, estrogens, CYP450.

« Previous Next »
Graphical Abstract

[1]
Marusyk, A.; Polyak, K. Tumor heterogeneity: causes and consequences. Biochim. Biophys. Acta, 2010, 1805(1), 105-117.
[PMID: 19931353]
[2]
Cancer - World Health Organization. Available at:. https://www.who.int/news-room/fact-sheets/detail/cancer
[3]
https://www.cancer.org/cancer/breast-cancer/about/how-common-is-breast-cancer.html
[4]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2019. CA Cancer J. Clin., 2019, 69(1), 7-34.
[http://dx.doi.org/10.3322/caac.21551] [PMID: 30620402]
[5]
Jordan, V.C. The new biology of estrogen-induced apoptosis applied to treat and prevent breast cancer. Endocr. Relat. Cancer, 2015, 22(1), R1-R31.
[http://dx.doi.org/10.1530/ERC-14-0448] [PMID: 25339261]
[6]
Jordan, V.C.; Furr, B.J. Recent progress in breast cancer research.Hormone therapy in breast and prostate cancer; Jordan, V.C; Furr, B.J., Ed.; Springer: Humana Press: New York, 2009, pp. 385-408.
[http://dx.doi.org/10.1007/978-1-59259-152-7_18]
[7]
Miller, W.R. Endocrine treatment for breast cancers: biological rationale and current progress. J. Steroid Biochem. Mol. Biol., 1990, 37(4), 467-480.
[http://dx.doi.org/10.1016/0960-0760(90)90390-7] [PMID: 2278830]
[8]
Yadav, M.R.; Barmade, M.A.; Tamboli, R.S.; Murumkar, P.R. Developing steroidal aromatase inhibitors-an effective armament to win the battle against breast cancer. Eur. J. Med. Chem., 2015, 105, 1-38.
[http://dx.doi.org/10.1016/j.ejmech.2015.09.038] [PMID: 26469743]
[9]
Thomas, M.P.; Potter, B.V. Discovery and development of the aryl O-sulfamate pharmacophore for oncology and women’s health. J. Med. Chem., 2015, 58(19), 7634-7658.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00386] [PMID: 25992880]
[10]
Miller, W.R. Background and development of aromatase inhibitors.Aromatase Inhibitors, Milestones in Drug Therapy; Furr, B.J., Ed.; Birkhäuser: Basel, 2008, pp. 1-21.
[http://dx.doi.org/10.1007/978-3-7643-8693-1_1]
[11]
Shoombuatong, W.; Schaduangrat, N.; Nantasenamat, C. Towards understanding aromatase inhibitory activity via QSAR modeling. EXCLI J., 2018, 17, 688-708.
[PMID: 30190660]
[12]
Cunningham, D.; Powles, T.J.; Dowsett, M.; Hutchison, G.; Brodie, A.M.; Ford, H.T.; Gazet, J.C.; Coombes, R.C. Oral 4-hydroxyandrostenedione, a new endocrine treatment for disseminated breast cancer. Cancer Chemother. Pharmacol., 1987, 20(3), 253-255.
[http://dx.doi.org/10.1007/BF00570496] [PMID: 3677299]
[13]
Dowsett, M.; Cunningham, D.C.; Stein, R.C.; Evans, S.; Dehennin, L.; Hedley, A.; Coombes, R.C. Dose-related endocrine effects and pharmacokinetics of oral and intramuscular 4-hydroxyandrostenedione in postmenopausal breast cancer patients. Cancer Res., 1989, 49(5), 1306-1312.
[PMID: 2917360]
[14]
MacNeill, F.A.; Jacobs, S.; Dowsett, M.; Lonning, P.E.; Powles, T.J. The effects of oral 4-hydroxyandrostenedione on peripheral aromatisation in post-menopausal breast cancer patients. Cancer Chemother. Pharmacol., 1995, 36(3), 249-254.
[http://dx.doi.org/10.1007/BF00685855] [PMID: 7781147]
[15]
Miller, W.R. Aromatase inhibitors and breast cancer. Cancer Treat. Rev., 1997, 23(3), 171-187.
[http://dx.doi.org/10.1016/S0305-7372(97)90037-2] [PMID: 9251721]
[16]
Lønning, P.E.; Jacobs, S.; Jones, A.; Haynes, B.; Powles, T.; Dowsett, M. The influence of CGS 16949A on peripheral aromatisation in breast cancer patients. Br. J. Cancer, 1991, 63(5), 789-793.
[http://dx.doi.org/10.1038/bjc.1991.175] [PMID: 1828173]
[17]
Demers, L.M.; Melby, J.C.; Wilson, T.E.; Lipton, A.; Harvey, H.A.; Santen, R.J. The effects of CGS 16949A, an aromatase inhibitor on adrenal mineralocorticoid biosynthesis. J. Clin. Endocrinol. Metab., 1990, 70(4), 1162-1166.
[PMID: 2156889]
[18]
Stein, R.C.; Dowsett, M.; Davenport, J.; Hedley, A.; Ford, H.T.; Gazet, J.C.; Coombes, R.C. Preliminary study of the treatment of advanced breast cancer in postmenopausal women with the aromatase inhibitor CGS 16949A. Cancer Res., 1990, 50(5), 1381-1384.
[PMID: 2137367]
[19]
Dutta, U.; Pant, K. Aromatase inhibitors: past, present and future in breast cancer therapy. Med. Oncol., 2008, 25(2), 113-124.
[http://dx.doi.org/10.1007/s12032-007-9019-x] [PMID: 17973095]
[20]
Plourde, P.V.; Dyroff, M.; Dukes, M. Arimidex: a potent and selective fourth-generation aromatase inhibitor. Breast Cancer Res. Treat., 1994, 30(1), 103-111.
[http://dx.doi.org/10.1007/BF00682745] [PMID: 7949201]
[21]
Demers, L.M.; Lipton, A.; Harvey, H.A.; Kambic, K.B.; Grossberg, H.; Brady, C.; Santen, R.J. The efficacy of CGS 20267 in suppressing estrogen biosynthesis in patients with advanced stage breast cancer. J. Steroid Biochem. Mol. Biol., 1993, 44(4-6), 687-691.
[http://dx.doi.org/10.1016/0960-0760(93)90283-3] [PMID: 8476785]
[22]
Iveson, T.J.; Smith, I.E.; Ahern, J.; Smithers, D.A.; Trunet, P.F.; Dowsett, M. Phase I study of the oral nonsteroidal aromatase inhibitor CGS 20267 in postmenopausal patients with advanced breast cancer. Cancer Res., 1993, 53(2), 266-270.
[PMID: 8417819]
[23]
di Salle, E.; Ornati, G.; Giudici, D.; Lassus, M.; Evans, T.R.J.; Coombes, R.C. Exemestane (FCE 24304), a new steroidal aromatase inhibitor. J. Steroid Biochem. Mol. Biol., 1992, 43(1-3), 137-143.
[http://dx.doi.org/10.1016/0960-0760(92)90198-R] [PMID: 1525055]
[24]
Coombes, R.C.; Kilburn, L.S.; Snowdon, C.F.; Paridaens, R.; Coleman, R.E.; Jones, S.E.; Jassem, J.; Van de Velde, C.J.H.; Delozier, T.; Alvarez, I.; Del Mastro, L.; Ortmann, O.; Diedrich, K.; Coates, A.S.; Bajetta, E.; Holmberg, S.B.; Dodwell, D.; Mickiewicz, E.; Andersen, J.; Lønning, P.E.; Cocconi, G.; Forbes, J.; Castiglione, M.; Stuart, N.; Stewart, A.; Fallowfield, L.J.; Bertelli, G.; Hall, E.; Bogle, R.G.; Carpentieri, M.; Colajori, E.; Subar, M.; Ireland, E.; Bliss, J.M. Survival and safety of exemestane versus tamoxifen after 2-3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet, 2007, 369(9561), 559-570.
[http://dx.doi.org/10.1016/S0140-6736(07)60200-1] [PMID: 17307102]
[25]
Augusto, T.V.; Correia-da-Silva, G.; Rodrigues, C.M.P.; Teixeira, N.; Amaral, C. Acquired resistance to aromatase inhibitors: where we stand! Endocr. Relat. Cancer, 2018, 25(5), R283-R301.
[http://dx.doi.org/10.1530/ERC-17-0425] [PMID: 29530940]
[26]
Narashimamurthy, J.; Rao, A.R.R.; Sastry, G.N. Aromatase inhibitors: a new paradigm in breast cancer treatment. Curr. Med. Chem. Anticancer Agents, 2004, 4(6), 523-534.
[http://dx.doi.org/10.2174/1568011043352669] [PMID: 15579017]
[27]
Simpson, E.R.; Dowsett, M. Aromatase and its inhibitors: significance for breast cancer therapy. Recent Prog. Horm. Res., 2002, 57, 317-338.
[http://dx.doi.org/10.1210/rp.57.1.317] [PMID: 12017550]
[28]
Brodie, A.M.; Njar, V.C. Aromatase inhibitors and their application in breast cancer treatment. Steroids, 2000, 65(4), 171-179.
[http://dx.doi.org/10.1016/S0039-128X(99)00104-X] [PMID: 10713305]
[29]
Smith, I.E.; Dowsett, M. Aromatase inhibitors in breast cancer. N. Engl. J. Med., 2003, 348(24), 2431-2442.
[http://dx.doi.org/10.1056/NEJMra023246] [PMID: 12802030]
[30]
Osborne, C.; Tripathy, D. Aromatase inhibitors: rationale and use in breast cancer. Annu. Rev. Med., 2005, 56, 103-116.
[http://dx.doi.org/10.1146/annurev.med.56.062804.103324] [PMID: 15660504]
[31]
Lønning, P.E. Estradiol measurement in translational studies of breast cancer. Steroids, 2015, 99(Pt A), 26-31.
[http://dx.doi.org/10.1016/j.steroids.2014.08.008] [PMID: 25159101]
[32]
Abul-Hajj, Y.J. Synthesis and evaluation of 4-(substituted thio)-4-androstene-3,17-dione derivatives as potential aromatase inhibitors. J. Med. Chem., 1986, 29(4), 582-584.
[http://dx.doi.org/10.1021/jm00154a025] [PMID: 3959033]
[33]
Abul-Hajj, Y.J. Aromatase inhibition by 4-thiosubstituted-4-androstene-3,17-dione derivatives. J. Steroid Biochem., 1990, 35(1), 139-143.
[http://dx.doi.org/10.1016/0022-4731(90)90158-O] [PMID: 2308324]
[34]
Abul-Hajj, Y.J.; Liu, X.P.; Hedge, M. Aromatase inhibitors: effect of ring A and ring B unsaturation on aromatase inhibition by 4-thiosubstituted derivatives of 4-androstene-3,17-dione. Steroids, 1995, 60(5), 423-427.
[http://dx.doi.org/10.1016/0039-128X(95)00020-Q] [PMID: 7570717]
[35]
Abul-Hajj, Y.J.; Liu, X.P.; Hedge, M. Synthesis and evaluation of 4-substituted-4-androstene-3,17-dione derivatives as aromatase inhibitors. J. Steroid Biochem. Mol. Biol., 1995, 54(3-4), 111-119.
[http://dx.doi.org/10.1016/0960-0760(95)00130-R] [PMID: 7662584]
[36]
Liu, X.P.; Lambert, D.M.; Abul-Hajj, Y.J. Probing the hydrophobic pocket of the active site of aromatase with 4-phenoxy-7 α-(phenylthio)-4-androstene-3,17-dione. J. Med. Chem., 1995, 38(20), 4135-4138.
[http://dx.doi.org/10.1021/jm00020a031] [PMID: 7562951]
[37]
Numazawa, M.; Tsuji, M.; Osawa, Y. Synthesis and evaluation of bromoacetoxy 4-androsten-3-ones as active site-directed inhibitors of human placental aromatase. Steroids, 1986, 48(5-6), 347-359.
[http://dx.doi.org/10.1016/0039-128X(86)90021-8] [PMID: 3445287]
[38]
Numazawa, M.; Oshibe, M. Further studies on 6-alkylandrost-4-ene-3,17-diones as aromatase inhibitors: elongation of the 6-alkyl chain. Steroids, 1995, 60(8), 506-511.
[http://dx.doi.org/10.1016/0039-128X(95)00058-X] [PMID: 8539792]
[39]
Numazawa, M.; Kamiyama, T.; Tachibana, M.; Oshibe, M. Synthesis and structure-activity relationships of 6-substituted androst-4-ene analogs as aromatase inhibitors. J. Med. Chem., 1996, 39(11), 2245-2252.
[http://dx.doi.org/10.1021/jm960047o] [PMID: 8667367]
[40]
Numazawa, M.; Oshibe, M.; Yamaguchi, S. 6-Alkylandrosta-4,6-diene-3,17-diones and their 1,4,6-triene analogs as aromatase inhibitors. Structure-activity relationships. Steroids, 1997, 62(8-9), 595-602.
[http://dx.doi.org/10.1016/S0039-128X(97)86814-6] [PMID: 9292934]
[41]
Numazawa, M.; Oshibe, M. 6-Alkyl- and 6-arylandrost-4-ene-3,17-diones as aromatase inhibitors. Synthesis and structure-activity relationships. J. Med. Chem., 1994, 37(9), 1312-1319.
[http://dx.doi.org/10.1021/jm00035a011] [PMID: 8176709]
[42]
Numazawa, M.; Yamada, K.; Nitta, S.; Sasaki, C.; Kidokoro, K. Role of hydrophilic interaction in binding of hydroxylated 3-deoxy C(19) steroids to the active site of aromatase. J. Med. Chem., 2001, 44(24), 4277-4283.
[http://dx.doi.org/10.1021/jm010282t] [PMID: 11708928]
[43]
Numazawa, M.; Yamada, K.; Watari, Y.; Ando, M. Improved synthesis and molecular modeling of 4β,19-dihydroxyandrost-5-en-17-one, an excellent inhibitor of aromatase. Chem. Pharm. Bull. (Tokyo), 2002, 50(5), 703-705.
[http://dx.doi.org/10.1248/cpb.50.703] [PMID: 12036037]
[44]
Numazawa, M.; Watari, Y.; Yamada, K.; Umemura, N.; Handa, W. Probing the active site of aromatase with 2-methyl-substituted androstenedione analogs. Steroids, 2003, 68(6), 503-513.
[http://dx.doi.org/10.1016/S0039-128X(03)00089-8] [PMID: 12906935]
[45]
Numazawa, M.; Handa, W.; Hasegawa, C.; Takahashi, M. Structure-activity relationships of 2α-substituted androstenedione analogs as aromatase inhibitors and their aromatization reactions. J. Steroid Biochem. Mol. Biol., 2005, 97(4), 353-359.
[http://dx.doi.org/10.1016/j.jsbmb.2005.06.029] [PMID: 16209922]
[46]
Numazawa, M.; Komatsu, S.; Tominaga, T.; Yamashita, K. Structure-activity relationships of estrogen derivatives as aromatase inhibitors. Effects of heterocyclic substituents. Chem. Pharm. Bull. (Tokyo), 2008, 56(9), 1304-1309.
[http://dx.doi.org/10.1248/cpb.56.1304] [PMID: 18758106]
[47]
Takahashi, M.; Handa, W.; Umeta, H.; Ishikawa, S.; Yamashita, K.; Numazawa, M. Aromatase inactivation by 2-substituted derivatives of the suicide substrate androsta-1,4-diene-3,17-dione. J. Steroid Biochem. Mol. Biol., 2009, 116(3-5), 191-199.
[http://dx.doi.org/10.1016/j.jsbmb.2009.05.015] [PMID: 19520161]
[48]
Takahashi, M.; Yamashita, K.; Numazawa, M. Probing the binding pocket of the active site of aromatase with 2-phenylaliphatic androsta-1,4-diene-3,17-dione steroids. Steroids, 2010, 75(4-5), 330-337.
[http://dx.doi.org/10.1016/j.steroids.2010.01.008] [PMID: 20096721]
[49]
Numazawa, M.; Tachibana, M.; Tateda, Y. 4-Oxygenated androst-5-en-17-ones and their 7-oxo derivatives as aromatase inhibitors. J. Steroid Biochem. Mol. Biol., 1996, 58(4), 431-438.
[http://dx.doi.org/10.1016/0960-0760(96)00066-0] [PMID: 8903428]
[50]
Nagaoka, M.; Watari, Y.; Yajima, H.; Tsukioka, K.; Muroi, Y.; Yamada, K.; Numazawa, M. Structure-activity relationships of 3-deoxy androgens as aromatase inhibitors. Synthesis and biochemical studies of 4-substituted 4-ene and 5-ene steroids. Steroids, 2003, 68(6), 533-542.
[http://dx.doi.org/10.1016/S0039-128X(03)00085-0] [PMID: 12906938]
[51]
Watari, Y.; Yamaguchi, S.; Takahashi, M.; Nagaoka, M.; Numazawa, M. 4- and 6-(p-Sulphamoylphenyl)androstenediones: Studies of aromatase inhibitor-based oestrone sulphatase inhibition. Steroids, 2010, 75(12), 891-896.
[http://dx.doi.org/10.1016/j.steroids.2010.05.011] [PMID: 20546769]
[52]
Brueggemeier, R.W.; Floyd, E.E.; Counsell, R.E. Synthesis and biochemical evaluation of inhibitors of estrogen biosynthesis. J. Med. Chem., 1978, 21(10), 1007-1011.
[http://dx.doi.org/10.1021/jm00208a002] [PMID: 722711]
[53]
Snider, C.E.; Brueggemeier, R.W. Potent enzyme-activated inhibition of aromatase by a 7 alpha-substituted C19 steroid. J. Biol. Chem., 1987, 262(18), 8685-8689.
[PMID: 3597393]
[54]
Li, P.K.; Brueggemeier, R.W. 7-substituted 1,4,6-androstatriene-3,17-diones as enzyme-activated irreversible inhibitors of aromatase. J. Steroid Biochem., 1990, 36(6), 533-539.
[http://dx.doi.org/10.1016/0022-4731(90)90170-W] [PMID: 2214770]
[55]
Li, P.K.; Brueggemeier, R.W. Synthesis and biochemical studies of 7-substituted 4,6-androstadiene-3,17-diones as aromatase inhibitors. J. Med. Chem., 1990, 33(1), 101-105.
[http://dx.doi.org/10.1021/jm00163a017] [PMID: 2296006]
[56]
Lovely, C.J.; Brueggemeier, R.W. Synthesis of 7α-substituted androstenediones by a 1,4-conjugate addition approach. Bioorg. Med. Chem. Lett., 1995, 5, 2513-2516.
[http://dx.doi.org/10.1016/0960-894X(95)00440-5]
[57]
O’Reilly, J.M.; Li, N.; Duax, W.L.; Brueggemeier, R.W. Synthesis, structure elucidation, and biochemical evaluation of 7 α- and 7 β-arylaliphatic-substituted androst-4-ene-3,17-diones as inhibitors of aromatase. J. Med. Chem., 1995, 38(15), 2842-2850.
[http://dx.doi.org/10.1021/jm00015a006] [PMID: 7636845]
[58]
O’Reilly, J.M.; Brueggemeier, R.W. 7α-Arylaliphatic androsta-1,4-diene-3,17-diones as enzyme-activated irreversible inhibitors of aromatase. J. Steroid Biochem. Mol. Biol., 1996, 59(1), 93-102.
[http://dx.doi.org/10.1016/S0960-0760(96)00087-8] [PMID: 9009242]
[59]
Darby, M.V.; Lovett, J.A.; Brueggemeier, R.W.; Groziak, M.P.; Counsell, R.E. 7 α-substituted derivatives of androstenedione as inhibitors of estrogen biosynthesis. J. Med. Chem., 1985, 28(6), 803-807.
[http://dx.doi.org/10.1021/jm00383a019] [PMID: 4009603]
[60]
Ebrahimian, S.; Chen, H.H.; Brueggemeier, R.W. Synthesis and biochemical studies of 7 α-substituted androsta-1,4-diene-3,17-diones as enzyme-activated irreversible inhibitors of aromatase. Steroids, 1993, 58(9), 414-422.
[http://dx.doi.org/10.1016/0039-128X(93)90081-W] [PMID: 8236327]
[61]
Bednarski, P.J.; Porubek, D.J.; Nelson, S.D. Thiol-containing androgens as suicide substrates of aromatase. J. Med. Chem., 1985, 28(6), 775-779.
[http://dx.doi.org/10.1021/jm00383a014] [PMID: 4009599]
[62]
Bednarski, P.J.; Nelson, S.D. Interactions of thiol-containing androgens with human placental aromatase. J. Med. Chem., 1989, 32(1), 203-213.
[http://dx.doi.org/10.1021/jm00121a037] [PMID: 2909733]
[63]
Shih, M.J.; Carrell, M.H.; Carrell, H.L.; Wright, C.L.; Johnston, J.N.; Robinson, C.H. Stereoselective inhibition of aromatase by novel epoxysteroids. J. Chem. Soc. Chem. Commun., 1987, 3, 213-214.
[http://dx.doi.org/10.1039/c39870000213]
[64]
Childers, W.E.; Robinson, C.H. Novel 10β-thiiranyl steroids as aromatase inhibitors. J. Chem. Soc. Chem. Commun., 1987, 5, 320-321.
[http://dx.doi.org/10.1039/C39870000320]
[65]
Wright, J.N.; Calder, M.R.; Akhtar, M. Steroidal C-19 sulphur and nitrogen derivatives designed as aromatase inhibitors. J. Chem. Soc. Chem. Commun., 1985, 23, 1733-1735.
[http://dx.doi.org/10.1039/c39850001733]
[66]
Cepa, M.M.; Tavares da Silva, E.J.; Correia-da-Silva, G.; Roleira, F.M.; Teixeira, N.A. Structure-activity relationships of new A,D-ring modified steroids as aromatase inhibitors: design, synthesis, and biological activity evaluation. J. Med. Chem., 2005, 48(20), 6379-6385.
[http://dx.doi.org/10.1021/jm050129p] [PMID: 16190763]
[67]
Cepa, M.; Correia-da-Silva, G.; Tavares da Silva, E.J.; Roleira, F.M.; Hong, Y.; Chen, S.; Teixeira, N.A. Molecular mechanisms of aromatase inhibition by new A, D-ring modified steroids. Biol. Chem., 2008, 389(9), 1183-1191.
[http://dx.doi.org/10.1515/BC.2008.134] [PMID: 18713005]
[68]
Cepa, M.M.; Tavares da Silva, E.J.; Correia-da-Silva, G.; Roleira, F.M.; Teixeira, N.A. Synthesis and biochemical studies of 17-substituted androst-3-enes and 3,4-epoxyandrostanes as aromatase inhibitors. Steroids, 2008, 73(14), 1409-1415.
[http://dx.doi.org/10.1016/j.steroids.2008.07.001] [PMID: 18691607]
[69]
Varela, C.; Tavares da Silva, E.J.; Amaral, C.; Correia da Silva, G.; Baptista, T.; Alcaro, S.; Costa, G.; Carvalho, R.A.; Teixeira, N.A.; Roleira, F.M. New structure-activity relationships of A- and D-ring modified steroidal aromatase inhibitors: design, synthesis, and biochemical evaluation. J. Med. Chem., 2012, 55(8), 3992-4002.
[http://dx.doi.org/10.1021/jm300262w] [PMID: 22475216]
[70]
Varela, C.L.; Amaral, C.; Correia-da-Silva, G.; Carvalho, R.A.; Teixeira, N.A.; Costa, S.C.; Roleira, F.M.; Tavares-da-Silva, E.J. Design, synthesis and biochemical studies of new 7α-allylandrostanes as aromatase inhibitors. Steroids, 2013, 78(7), 662-669.
[http://dx.doi.org/10.1016/j.steroids.2013.02.016] [PMID: 23499824]
[71]
Varela, C.L.; Amaral, C.; Tavares da Silva, E.; Lopes, A.; Correia-da-Silva, G.; Carvalho, R.A.; Costa, S.C.; Roleira, F.M.; Teixeira, N. Exemestane metabolites: Synthesis, stereochemical elucidation, biochemical activity and anti-proliferative effects in a hormone-dependent breast cancer cell line. Eur. J. Med. Chem., 2014, 87, 336-345.
[http://dx.doi.org/10.1016/j.ejmech.2014.09.074] [PMID: 25277066]
[72]
Varela, C.L.; Amaral, C.; Correia-da-Silva, G.; Costa, S.C.; Carvalho, R.A.; Costa, G.; Alcaro, S.; Teixeira, N.A.; Tavares-da-Silva, E.J.; Roleira, F.M. Exploring new chemical functionalities to improve aromatase inhibition of steroids. Bioorg. Med. Chem., 2016, 24(12), 2823-2831.
[http://dx.doi.org/10.1016/j.bmc.2016.04.056] [PMID: 27160054]
[73]
Amaral, C.; Varela, C.L.; Maurício, J.; Sobral, A.F.; Costa, S.C.; Roleira, F.M.F.; Tavares-da-Silva, E.J.; Correia-da-Silva, G.; Teixeira, N. Anti-tumor efficacy of new 7α-substituted androstanes as aromatase inhibitors in hormone-sensitive and resistant breast cancer cells. J. Steroid Biochem. Mol. Biol., 2017, 171, 218-228.
[http://dx.doi.org/10.1016/j.jsbmb.2017.04.002] [PMID: 28396197]
[74]
Roleira, F.M.F.; Varela, C.; Amaral, C.; Costa, S.C.; Correia-da-Silva, G.; Moraca, F.; Costa, G.; Alcaro, S.; Teixeira, N.A.A.; Tavares da Silva, E.J. C-6α-vs C-7α-substituted steroidal aromatase inhibitors: which is better? synthesis, biochemical evaluation, docking studies, and structure–activity relationships. J. Med. Chem., 2019, 62(7), 3636-3657.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00157] [PMID: 30852901]
[75]
Yadav, M.R.; Sabale, P.M.; Giridhar, R.; Zimmer, C.; Haupenthal, J.; Hartmann, R.W. Synthesis of some novel androstanes as potential aromatase inhibitors. Steroids, 2011, 76(5), 464-470.
[http://dx.doi.org/10.1016/j.steroids.2010.12.013] [PMID: 21215765]
[76]
Yadav, M.; Sabale, P.; Giridhar, R.; Baria, D.; Zimmer, C.; Hartmann, R. Synthesis and preliminary screening of novel A-and D-ring modified steroids as aromatase inhibitors. Lett. Drug Des. Discov., 2011, 8, 943-950.
[http://dx.doi.org/10.2174/157018011797655322]
[77]
Yadav, M.R.; Sabale, P.M.; Giridhar, R.; Zimmer, C.; Hartmann, R.W. Steroidal carbonitriles as potential aromatase inhibitors. Steroids, 2012, 77(8-9), 850-857.
[http://dx.doi.org/10.1016/j.steroids.2012.04.010] [PMID: 22546985]
[78]
Yadav, M.R.; Sabale, P.M.; Murumkar, P.R.; Giridhar, R. 4- (Arylthia)- 16ξ-cyano-17-oxo-4-androsten-3-ones, reduced derivatives 17β-ols and the process for their preparation. IND Patent, 3137402019,
[79]
Barigye, S.J.; Freitas, M.P.; Ausina, P.; Zancan, P.; Sola-Penna, M.; Castillo-Garit, J.A. Discrete Fourier transform-based multivariate image analysis: application to modeling of aromatase inhibitory activity. ACS Comb. Sci., 2018, 20(2), 75-81.
[http://dx.doi.org/10.1021/acscombsci.7b00155] [PMID: 29297675]
[80]
Lone, S.H.; Bhat, M.A.; Lone, R.A.; Jameel, S.; Lone, J.A.; Bhat, K.A. Hemisynthesis, computational and molecular docking studies of novel nitrogen containing steroidal aromatase inhibitors: testolactam and testololactam. New J. Chem., 2018, 42, 4579-4589.
[http://dx.doi.org/10.1039/C8NJ00063H]
[81]
Martin, G.D.; Narvaez, J.; Marti, A. Synthesis and bioconversions of formestane. J. Nat. Prod., 2013, 76(10), 1966-1969.
[http://dx.doi.org/10.1021/np400585t] [PMID: 24074257]
[82]
Martin, G.D.; Narvaez, J.; Bulmer, R.; Durrant, M.C. Biotransformation and molecular docking studies of aromatase inhibitors. Steroids, 2016, 113, 95-102.
[http://dx.doi.org/10.1016/j.steroids.2016.07.003] [PMID: 27421190]
[83]
Lee, S.; Barron, M.G. 3D-QSAR study of steroidal and azaheterocyclic human aromatase inhibitors using quantitative profile of protein-ligand interactions. J. Cheminform., 2018, 10(1), 2.
[http://dx.doi.org/10.1186/s13321-017-0253-8] [PMID: 29349513]

Rights & Permissions Print Cite
Article Metrics
10
© 2024 Bentham Science Publishers | Privacy Policy