DOCKING STUDIES OF SUBSTITUTED CHROMAN ANALOGS AT ESTROGEN RECEPTOR
Abstract
Objective: The objective of the present study is to perform the molecular docking studies of some newly designed chroman analogs on estrogen
receptor (ER) (PDB: 1YIM) by Glide v5.0.
Methods: The docking studies of designed chroman analogs were performed on the active site of ER (PDB: 1YIM) for anti-breast cancer activity using
Schrodinger Glide v5.0. Absorption, distribution, metabolism, excretion properties of all designed compounds were also calculated by Qik Prop v3. 0.
Results: Among all compounds, compound 38 showed highest docking score (−8.17) in the series. Docking scores were compared with standard
drugs tamoxifene (−11.08) and anastrazole (−7.86). All compounds were found to be within expectable range for percent human oral absorption,
octanol/water partition coefficient (QP log Po/w), brain/blood partition coefficient (QP log BB), total solvent accessible surface area, and rule of five
predicted by Qikprop.
Conclusion: Most of the compounds in the series showed good molecular docking score on the ER (PDB: 1YIM). Compound 38 (−8.16) exhibited
better docking score than standard drug anastrazole (−7.86). Most of the pharmacokinetic properties conducted by Qikprop were found to be within
the permissible range.
Keywords: Chroman, Docking, Estrogen receptor, Lipinski's rule of five.
Downloads
References
Purushothaman A, Nandhakumar E, Sachdanandam P. Anticancer effect
of shemamruthaa (a phytochemical formulation) on 7, 12-dimethylbenz
(a) anthracene induced mammary carcinoma in rats. Asian J Pharm Clin
Res 2012;5(1):101-7.
Bonfield K, Amato E, Bankemper T, Agard H, Steller J, Keeler JM, et al.
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):2603-13.
Nam JM, Jeon KH, Kwon H, Lee E, Jun KY, Jin YB, et al.
Dithiiranylmethyloxy azaxanthone shows potent anti-tumor activity
via suppression of HER2 expression and HER2-mediated signals
in HER2-overexpressing breast cancer cells. Eur J Pharm Sci
;50(2):181-90.
Tan Q, Blizzard TA, Morgan JD nd, Birzin ET, Chan W, Yang YT, et al.
Estrogen receptor ligands. Part 10: Chromanes: Old scaffolds for new
SERAMs. Bioorg Med Chem Lett 2005;15(6):1675-81.
Gupta A, Dwivedy A, Keshri G, Sharma R, Balapure AK, Singh MM,
et al. Rapid synthesis of 4-benzylidene and 4-[bis-(4-methoxyphenyl)methylene-2-substituted
phenyl-benzopyrans
as potential selective
estrogen
receptor modulators
(SERMs) using McMurry coupling
reaction.
Bioorg
Med Chem Lett 2006;16(23):6006-12.
Reddy BV, Divya B, Swaina M, Rao TP, Yadav JS, Vardhan MV.
A domino Knoevenagel hetero-Diels–Alder reaction for the synthesis
of polycyclic chromene derivatives and evaluation of their cytotoxicity.
Bioorg Med Chem Lett 2012;22(5):1995-9.
Wang D, Chuang HC, Weng SC, Huang PH, Hsieh HY, Kulp SK, et
al. α-Tocopheryl succinate as a scaffold to develop potent inhibitors of
breast cancer cell adhesion. J Med Chem 2009;52(18):5642-8.
Miller WR. Aromatase inhibitors: Mechanism of action and role in the
treatment of breast cancer. Semin Oncol 2003;30:3-11.
Florence X, Dilly S, Tullio PD, Pirotte B, Lebrun P. Modulation
of the 6-position of benzopyran derivatives and inhibitory
effects on the insulin releasing process. Bioorg Med Chem
;19(13):3919-28.
Conti C, Monaco LP, Desideri N. Design, synthesis and in vitro
evaluation of novel chroman-4-one, chroman, and 2H-chromene
derivatives as human rhinovirus capsid-binding inhibitors. Bioorg Med
Chem 2011;19(24):7357-64.
Koufaki M, Kiziridi C, Alexi X, Alexis MN. Design and synthesis of
novel neuroprotective 1,2 dithiolane/chroman hybrids. Bioorg Med
Chem 2009;17(17):6432-41.
Kanbe Y, Kim MH, Nishimoto M, Ohtake Y, Kato N, Tsunenari T,
et al. Discovery of thiochroman and chroman derivatives as pure
antiestrogens and their structure-activity relationship. Bioorg Med
Chem 2006;14(14):4803-19.
Lee H, Lee K, Jung JK, Cho J, Theodorakis EA. Synthesis and evaluation
of 6-hydroxy-7-methoxy-4-chromanone- and chroman-2-carboxamides
as antioxidants. Bioorg Med Chem Lett 2005;15(11):2745-8.
Shen Z, Ramamoorthy SP, Hatzenbuhler NT, Evrard DA, Childers W,
Harrison BL, et al. Synthesis and structure-activity relationship of
novel lactam-fused chroman derivatives having dual affinity at the
-HT1A receptor and the serotonin transporter. Bioorg Med Chem Lett
;20(1):222-7.
Kraus GA, Mengwasser J, Maury W, Oh C. Synthesis of
chroman aldehydes that inhibit HIV. Bioorg Med Chem Lett
;21(5):1399-401.
Koufaki M, Kiziridi C, Papazafiri P, Vassilopoulos A, Varro A, Nagy Z,
et al. Synthesis and biological evaluation of benzopyran analogues
bearing class III antiarrhythmic pharmacophores. Bioorg Med Chem
;14(19):6666-78.
Thompson R, Doggrell S, Hoberga JO. Potassium channel activators
based on the benzopyran substructure: Synthesis and activity of the C-8
substituent. Bioorg Med Chem 2003;11(8):1663-8.
Schrodinger LLC. New York, USA: Schrodinger Inc.; 2008. http://
www.schrodinger.com.
Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT,
et al. Glide: A new approach for rapid, accurate docking and
scoring. Method and assessment of docking accuracy. J Med Chem
;47(7):1739-49.
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental
and computational approaches to estimate solubility and permeability
in drug discovery and development settings. Adv Drug Deliv Rev
;64(1-3):4-17.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.