Estrogen, the key regulator of the cellular process involved in the development and maintenance of reproductive functions, mediates its action through estrogen receptor binding, and initiating a series of cellular pathway producing estrogen-induced responses. At higher dose, it can effectively act as contraceptive but associates with risk factors. Considering the long-term benefit-to-risk ratio of estrogen analogs as oral contraceptives, the present in-silico study has been focussed to deduce the active pharmacophore features required to differentiate the anti-fertility potency from estrogenic activity of steroidal motif. Hydrophobicity is an essential property for promoting both the functionalities, but molecular conformation and presence of hydrogen bond acceptors have been deduced to be the distinguishing features of anti-fertility activity of estrogen analogs as revealed from the molecular field and similarity analyses, and receptor-dependent docking studies.

ACHINTYA SAHA

Chemical Technology

RIA PAL

MD ATAUL ISLAM

TABASSUM HOSSAIN

University of Calcutta (informally known as Calcutta University or CU) is a collegiate public state university located in Kolkata, West Bengal, India.&nbsp;Within India it is recognized as a &quot;Five-Star University&quot; and accredited &quot;A&quot; Grade by National Assessment and Accreditation Council.

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The University of Calcutta has secured the Fifth position among the Universities of India in the prestigious &quot;Indian University Ranking 2019&quot; list, released by the NIRF of the Ministry of Human Resource Development, Government of India.

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It was established on 24 January 1857, and was one of the first institutions in Asia to be established as a multidisciplinary and Western-style university. Its alumni and faculty include several heads of state, heads of government, social reformers, prominent artists, only academy award winner and Dirac medal winner in India, many Fellows of the Royal Society and five Nobel laureates as of 2019 which is highest in South Asia.

University Of Calcutta

Molecular Mapping and Docking Interactions for Selective Anti-Fertility Potency of Estrogen Analogs

Letters in Drug Design and Discovery

Estrogen mediates its action following binding to the estrogen receptor to form an estrogen-receptor complex. The complex initiates gene transcription and produces estrogen-induced cell and/or tissue responses, i.e., estrogenic actions. High doses of estrogen can be used effectively as a contraceptive but are associated with side effects. Considering the long-term benefit-to-risk ratio of estrogen analogs as oral contraceptives, the present study was performed to deduce the active pharmacophore features required to differentiate the anti-fertility potency from the estrogenic activity of the steroidal motif. Implementing classical quantitative structure-activity relationship (QSAR) studies, substitution by an electron-donating group at the C17 position and the presence of a hydrogen bond acceptor at C11, along with the orientation and conformational rigidity of the molecule, were found to be critically important features for estrogenic potency, including anti-fertility activity. However, low electron density at C2 and high electronegativity at C16, which may be due to substitution on those and/or neighboring atoms, favor contraceptive potency, whereas high electron density at C5 and substitution by an electron-withdrawing group at C7, which may confer hydrophobicity on the steroidal scaffold and an overall increment of electron affinity of the molecule, are favorable for estrogenicity. Further CATALYST-based 3D space modeling demonstrates that the presence of the aromatic ring (ring A), hydrophobic zone (ring B), and hydrogen bond acceptor at C17 in ring D, along with steric influence due to conformational rigidity of the compound, impart estrogenic contraceptive activity, but the presence of a second acceptor in ring A, and the critical distances between these features, selectively differentiate the anti-fertility potency from the estrogenic activity. © Springer-Verlag 2008.

Journal of Molecular Modeling

Pharmacophore search for anti-fertility and estrogenic potencies of estrogen analogs

Considering the worth of developing non-steroidal estrogen analogues, the present research explores the pharmacophores of 1-trifluoromethyl-1,2,2- triphenylethylenes (Fig. 1) for post-coital antifertility activity using electrotopological state atom (E-state) index. The study shows the efficacy of E-state index in developing statistically acceptable model, which explains the electronic environment and topological states of different atoms in a molecule. The exploration concluded that phenyl ring attached to an ethylenic moiety, para substitution by nucleophilic group on the phenyl ring and presence of strong electronegative group as the 4th substituent on the 1st carbon of the ethylenic moiety might be crucial for activity. © 2003 Elsevier Ltd. All rights reserved.

Bioorganic and Medicinal Chemistry Letters

Predicting pharmacophore signals for post-coital antifertility activity of 1-trifluoromethyl-1,2,2-triphenylethylene derivatives: A statistical approximation using E-state index

Rang &amp;amp Dale's Pharmacology

The reproductive system

European Journal of Medicinal Chemistry

Pharmacophore based virtual screening, molecular docking studies to design potent heat shock protein 90 inhibitors

Nature Chemical Biology

Coupling of receptor conformation and ligand orientation determine graded activity

Journal	Letters in Drug Design and Discovery
Publisher	BENTHAM SCIENCE PUBL LTD
ISSN	1570-1808