Identification of structural requirements of estrogen receptor modulators using pharmacoinformatics techniques for application to estrogen therapy

详细信息    查看全文

• 作者：Md. Ataul Islam ; Darshakkumar Ashokbhai Patel…
• 关键词：Estrogen receptor ; SERMs ; QSAR ; Pharmacophore ; Molecular Docking
• 刊名：Medicinal Chemistry Research
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：25
• 期：3
• 页码：407-421
• 全文大小：1,803 KB
• 参考文献：Accelrys (2013) Discovery studio modeling environment, Release 4.0. Accelrys Software Inc., San Diego
  Balaban AT, Khadikar PV, Supuran CT, Thakur A, Thakur M (2005) Study on supramolecular complexing ability vis-a-vis estimation of pKa of substituted sulfonamides: dominating role of Balaban index (J). Bioorg Med Chem Lett 15:3966–3973. doi:10.​1016/​j.​bmcl.​2005.​05.​136 CrossRef PubMed
  Berman HM et al. (2000) The protein data bank. Nucl Acids Res 28:235–242PubMedCentral CrossRef PubMed
  Brogia S, Papazafiric P, Roussisd V, Tafi A (2013) 3D-QSAR using pharmacophore-based alignment and virtual screening for discovery of novel MCF-7 cell line inhibitors. Eur J Med Chem 67:344–351CrossRef
  Burrow PD, Modelli A (2013) On the treatment of LUMO energies for their use as descriptors. SAR QSAR Environ Res 24:647–659. doi:10.​1080/​1062936X.​2013.​792873 CrossRef PubMed
  Chang YH, Chen JY, Hor CY, Chuang YC, Yang CB, Yang CN (2013) Computational study of estrogen receptor-alpha antagonist with three-dimensional quantitative structure–activity relationship support vector regression, and linear regression methods. Int J Med Chem 2013:1–3
  Chlebowski RT et al. (2003) Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the women’s health initiative randomized trial. JAMA 289:3243–3253. doi:10.​1001/​jama.​289.​24.​3243 CrossRef PubMed
  Chmel R, Rob L, Strnad P (2002) [What can we expect of raloxifene in the treatment of postmenopausal osteoporosis–views of a gynecologist] Ceska gynekologie/Ceska lekarska spolecnost J Ev Purkyne 67:187–191
  Clarke R et al. (2003) Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling. Oncogene 22:7316–7339. doi:10.​1038/​sj.​onc.​1206937 CrossRef PubMed
  Cramer RD, Patterson DE, Bunce JD (1988) Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J Am Chem Soc 110:5959–5967. doi:10.​1021/​ja00226a005 CrossRef PubMed
  Dalkas GA, Vlachakis D, Tsagkrasoulis D, Kastania A, Kossida S (2012) State-of-the-art technology in modern computer-aided drug design Brifiefings. Bioinformatics 14:745–752PubMed
  Doisneau-Sixou SF, Sergio CM, Carroll JS, Hui R, Musgrove EA, Sutherland RL (2003) Estrogen and antiestrogen regulation of cell cycle progression in breast cancer cells. Endocr Relat Cancer 10:179–186CrossRef PubMed
  Dowers TS, Qin ZH, Thatcher GR, Bolton JL (2006) Bioactivation of selective estrogen receptor modulators (SERMs). Chem Res Toxicol 19:1125–1137. doi:10.​1021/​tx060126v PubMedCentral CrossRef PubMed
  Fisher B et al. (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90:1371–1388CrossRef PubMed
  Fisher B et al. (2005) Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 97:1652–1662. doi:10.​1093/​jnci/​dji372 CrossRef PubMed
  Foster JS, Henley DC, Ahamed S, Wimalasena J (2001a) Estrogens and cell-cycle regulation in breast cancer. Trends Endocrinol Metab TEM 12:320–327CrossRef PubMed
  Foster JS, Henley DC, Bukovsky A, Seth P, Wimalasena J (2001b) Multifaceted regulation of cell cycle progression by estrogen: regulation of Cdk inhibitors and Cdc25A independent of cyclin D1-Cdk4 function. Mol Cell Biol 21:794–810. doi:10.​1128/​MCB.​21.​3.​794-810.​2001 PubMedCentral CrossRef PubMed
  Gehrig PA, Bae-Jump VL, Boggess JF, Groben PA, Fowler WC Jr, Van Le L (2004) Association between uterine serous carcinoma and breast cancer. Gynecol Oncol 94:208–211. doi:10.​1016/​j.​ygyno.​2004.​04.​009 CrossRef PubMed
  Golbraikh A, Tropsha A (2002) Beware of q2! J Mol Graph Model 20:269–276CrossRef PubMed
  Gupta MK, Prabhakar YS (2008) QSAR study on tetrahydroquinoline analogues as plasmodium protein farnesyltransferase inhibitors: a comparison of rationales of malarial and mammalian enzyme inhibitory activities for selectivity. Eur J Med Chem 43:2751–2767. doi:10.​1016/​j.​ejmech.​2008.​01.​025 CrossRef PubMed
  Gustafsson JA (1999) Estrogen receptor beta—a new dimension in estrogen mechanism of action. J Endocrinol 163:379–383CrossRef PubMed
  Holst F et al. (2007) Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer. Nat Genet 39:655–660. doi:10.​1038/​ng2006 CrossRef PubMed
  Hopfinger AJ, Tokarski JS (1997) Three-dimensional quantitative structure–activity relationship analysis. In: Charifson PS (ed) Practical application of computer-aided drug design. MarcelDekker Inc, New York, pp 105–164
  Islam MA, Nagar S, Das S, Mukherjee A, Saha A (2008) Molecular design based on receptor-independent pharmacophore: application to estrogen receptor ligands. Biol Pharm Bull 31:1453–1460CrossRef PubMed
  Kapetanovic IM (2008) Computer-aided drug discovery and development (CADDD): in silico-chemico-biological approach. Chem Biol Interact 171:165–176. doi:10.​1016/​j.​cbi.​2006.​12.​006 PubMedCentral CrossRef PubMed
  Kim Y, Nam NH, You YJ, Ahn BZ (2002) Synthesis and cytotoxicity of 3,4-diaryl-2(5H)-furanones. Bioorg Med Chem Lett 12:719–722CrossRef PubMed
  Kristam R, Gillet VJ, Lewis RA, Thorner D (2005) Comparison of conformational analysis techniques to generate pharmacophore hypotheses using catalyst. J Chem Inf Model 45:461–476. doi:10.​1021/​ci049731z CrossRef PubMed
  Kubinyi H (2004) 2D QSAR models: Hansch and Free-Wilson analyses. In: Bultinck P, Winter HD, Langenaeker W, Tollenaere JP (eds) Computer medicinal chemistry drug discovery. Marcel Dekker Inc, NewYork, pp 539–570
  Kubinyi H, Hamprecht FA, Mietzner T (1998) Three-dimensional quantitative similarity-activity relationships (3D QSiAR) from SEAL similarity matrices. J Med Chem 41:2553–2564. doi:10.​1021/​jm970732a CrossRef PubMed
  Kupcewicz B, Balcerowska-Czerniak G, Malecka M, Paneth P, Krajewska U, Rozalski M (2013) Structure-cytotoxic activity relationship of 3-arylideneflavanone and chromanone (E, Z isomers) and 3-arylflavones. Bioorg Med Chem Lett 23:4102–4106. doi:10.​1016/​j.​bmcl.​2013.​05.​044 CrossRef PubMed
  Levet A et al. (2013) Quantitative structure-activity relationship to predict acute fish toxicity of organic solvents. Chemosphere 93:1094–1103. doi:10.​1016/​j.​chemosphere.​2013.​06.​002 CrossRef PubMed
  Lewis JS, Jordan VC (2005) Selective estrogen receptor modulators (SERMs): mechanisms of anticarcinogenesis and drug resistance. Mutat Res 591:247–263. doi:10.​1016/​j.​mrfmmm.​2005.​02.​028 CrossRef PubMed
  Lewis DF, Parker MG, King RJ (1995) Molecular modelling of the human estrogen receptor and ligand interactions based on site-directed mutagenesis and amino acid sequence homology. J Steroid Biochem Mol Biol 52:55–65CrossRef PubMed
  Li H, Sutter J, Hoffman R (2000) Pharmacophore perception, development, and use in drug design. International University Line, California
  Maximov PY, Lee TM, Jordan VC (2013) The discovery and development of selective estrogen receptor modulators (SERMs) for clinical practice. Curr Clin Pharmacol 8:135–155PubMedCentral CrossRef PubMed
  Mitra I, Saha A, Roy K (2010) Pharmacophore mapping of arylamino-substituted benzo[b]thiophenes as free radical scavengers. J Mol Model 16:1585–1596. doi:10.​1007/​s00894-010-0661-4 CrossRef PubMed
  MOE (2007) Molecular operating environment (MOE). Chemical Computing Group Inc., 1010 Sherbooke St. West, Suite #910, Montreal, QC, Canada
  Mukherjee S, Saha A, Roy K (2005) QSAR of estrogen receptor modulators: exploring selectivity requirements for ER(alpha) versus ER(beta) binding of tetrahydroisoquinoline derivatives using E-state and physicochemical parameters. Bioorg Med Chem Lett 15:957–961. doi:10.​1016/​j.​bmcl.​2004.​12.​048 CrossRef PubMed
  Nandy A, Kar S, Roy K (2013) Development and validation of regression-based QSAR models for quantification of contributions of molecular fragments to skin sensitization potency of diverse organic chemicals. SAR QSAR Environ Res 24:1009–1023. doi:10.​1080/​1062936X.​2013.​821422 CrossRef PubMed
  Nantasenamat C, Worachartcheewan A, Prachayasittikul S, Isarankura-Na-Ayudhya C, Prachayasittikul V (2013) QSAR modeling of aromatase inhibitory activity of 1-substituted 1,2,3-triazole analogs of letrozole. Eur J Med Chem 69:99–114. doi:10.​1016/​j.​ejmech.​2013.​08.​015 CrossRef PubMed
  Ojha PK, Mitra I, Das RN, Roy K (2011) Further exploring rm2 metrics for validation of QSPR models. Chemometr Intell Lab Syst 107:194–205CrossRef
  Pickar JH, MacNeil T, Ohleth K (2010) SERMs progress and future perspectives. Maturitas 67:129–138. doi:10.​1016/​j.​maturitas.​2010.​05.​009 CrossRef PubMed
  Pike VW, Law MP, Osman S, Davenport RJ, Rimoldi O, Giardina D, Camici PG (2000) Selection, design and evaluation of new radioligands for PET studies of cardiac adrenoceptors. Pharm Acta Helv 74:191–200CrossRef PubMed
  Platts JA, Oldfield SP, Reif MM, Palmucci A, Gabano E, Osella D (2006) The RP-HPLC measurement and QSPR analysis of logP(o/w) values of several Pt(II) complexes. J Inorg Biochem 100:1199–1207. doi:10.​1016/​j.​jinorgbio.​2006.​01.​035 CrossRef PubMed
  Rastija V, Medic-Saric M (2009) QSAR study of antioxidant activity of wine polyphenols. Eur J Med Chem 44:400–408. doi:10.​1016/​j.​ejmech.​2008.​03.​001 CrossRef PubMed
  Richardson TI, Dodge JA, Wang Y, Durbin JD, Krishnan V, Norman BH (2007) Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 5: combined A- and C-ring structure-activity relationship studies. Bioorg Med Chem Lett 17:5563–5566. doi:10.​1016/​j.​bmcl.​2007.​08.​009 CrossRef PubMed
  Riggs BL, Hartmann LC (2003) Selective estrogen-receptor modulators—mechanisms of action and application to clinical practice. N Engl J Med 348:618–629. doi:10.​1056/​NEJMra022219 CrossRef PubMed
  Rossouw JE et al. (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. Jama 288:321–333CrossRef PubMed
  Roy PP, Roy K (2008) On some aspects of variable selection for partial least squares regression models. QSAR Comb Sci 27:302–313CrossRef
  Roy PP, Paul S, Mitra I, Roy K (2009) On two novel parameters for validation of predictive QSAR models. Molecules 14:1660–1701CrossRef PubMed
  Roy K, Mitra I, Kar S, Ojha PK, Das RN, Kabir H (2012) Comparative studies on some metrics for external validation of QSPR models. J Chem Inf Model 52:396–408. doi:10.​1021/​ci200520g CrossRef PubMed
  Sadler BR, Cho SJ, Ishaq KS, Chae K, Korach KS (1998) Three-dimensional quantitative structure-activity relationship study of nonsteroidal estrogen receptor ligands using the comparative molecular field analysis/cross-validated r2-guided region selection approach. J Med Chem 41:2261–2267. doi:10.​1021/​jm9705521 CrossRef PubMed
  Saxena AK et al. (2003) QSAR studies in substituted 1,2,3,4,6,7,12,12a-octa-hydropyrazino[2’,1’:6,1]pyrido[3,4-b]indoles–a potent class of neuroleptics. Bioorg Med Chem 11:2085–2090CrossRef PubMed
  Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA, Greene GL (1998) The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell 95:927–937CrossRef PubMed
  Smith HM, Knox AJ, Zisterer DM, Lloyd DG, Meegan MJ (2007) Flexible estrogen receptor modulators: synthesis, biochemistry and molecular modeling studies for 3-benzyl-4,6-diarylhex-3-ene and 3,4,6-triarylhex-3-ene derivatives. Med Chem 3:135–155CrossRef PubMed
  Snedecor GW, Cochran WG (1967) Statistical methods Ames, 6th edn. State University Press, Iowa
  Vedani A, Dobler M (2002) Multidimensional QSAR: moving from three- to five-dimensional concepts. Quant Struct Act Relat 21:382–390CrossRef
  Verma J, Khedkar VM, Coutinho EC (2010) 3D-QSAR in drug design—a review. Curr Top Med Chem 10:95–115CrossRef PubMed
  Wang P et al. (2012) Identification and structure-activity relationships of a novel series of estrogen receptor ligands based on 7-thiabicyclo[2.2.1]hept-2-ene-7-oxide. J Med Chem 55:2324–2341. doi:10.​1021/​jm201556r PubMedCentral CrossRef PubMed
  Wildman SA, Crippen GM (1999) Prediction of physicochemical parameters by atomic contributions. J Chem Inf Model 39:868–873CrossRef
  Yaffe K, Sawaya G, Lieberburg I, Grady D (1998) Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. Jama 279:688–695CrossRef PubMed
  Zhang L et al. (2013) Identification of putative estrogen receptor-mediated endocrine disrupting chemicals using QSAR- and structure-based virtual screening approaches. Toxicol Appl Pharmacol 272:67–76. doi:10.​1016/​j.​taap.​2013.​04.​032 PubMedCentral CrossRef PubMed
  
• 作者单位：Md. Ataul Islam (1) (4)
  Darshakkumar Ashokbhai Patel (2)
  Savansinh Ghanshyamsinh Rathod (2)
  Preeti Chunarkar (3)
  Tahir S. Pillay (1) (4) (5)
  
  1. Department of Chemical Pathology, Faculty of Health Sciences, University of Pretoria, Private Bag X323, Arcadia, Pretoria, 0007, South Africa
  4. National Health Laboratory Service, Tshwane Academic Division, Pretoria, South Africa
  2. G.H.Patel Post Graduate Department of Computer Science and Technology (GDCST), Sardar Patel University, Anand, Gujarat, India
  3. Department of Bioinformatics, Rajiv Gandhi Institute of Information Technology and Biotechnology, Bharati Vidyapeeth Deemed University, Pune-Satara Road, Pune, India
  5. Division of Chemical Pathology, Faculty of Health Sciences, University of Cape Town, Rondebosch, Cape Town, South Africa
  
• 刊物主题：Pharmacology/Toxicology; Biochemistry, general; Cell Biology;
• 出版者：Springer US
• ISSN：1554-8120

文摘

In this study, we explored the structural requirements of known estrogen receptor modulators for biological activity using pharmacoinformatics approaches to elucidate critical functionalities for new, potent and less toxic chemical agents for successful application in estrogen therapy. For this purpose, a group of nonsteroidal ligands 7-thiabicyclo[2.2.1]hept-2-ene-7-oxide derivatives were collected from the literature to perform quantitative structure–activity relationship (QSAR), pharmacophore and molecular docking studies. The 2D QSAR models (R _α 2  = 0.857, se _α  = 0.370, Q _α 2  = 0.848, R _pred−α 2  = 0.675, s _pα  = 0.537; R _β 2  = 0.874, se _β  = 0.261, Q _β 2  = 0.859, R _pred−β 2  = 0.659, s _pβ  = 0.408) explained that hydrophobicity and molar refractivity were crucial for binding affinity in both α- and β-subtypes. The space modeling study (R _α 2  = 0.955, se _α  = 1.311, Q _α 2  = 0.932, R _pred−α 2  = 0.737, s _pα  = 0.497; R _β 2  = 0.885, se _β  = 1.328, Q _β 2  = 0.878, R _pred−β 2  = 0.769, s _pβ  = 0.336) revealed the importance of HB donor and hydrophobic features for both subtypes, whereas HB acceptor and aromatic ring were critical for α- and β-subtypes, respectively. The functionalities developed in the QSAR and pharmacophore studies were substantiated by molecular docking studies which provided the preferred orientation of ligands for effective interaction at the active site cavity. Keywords Estrogen receptor SERMs QSAR Pharmacophore Molecular Docking