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Biological Activity of Sporolides A and B from Salinispora tropica : in silico Target Prediction Using Ligand‐Based Pharmacophore Mapping and in vitro activity Validation on HIV ‐1 Reverse Transcriptase
Author(s) -
Dineshkumar Kesavan,
Aparna Vasudevan,
Madhuri Kantilal Z.,
Hopper Waheeta
Publication year - 2014
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12252
Subject(s) - pharmacophore , reverse transcriptase , in silico , docking (animal) , in vitro , chemistry , computational biology , ligand (biochemistry) , biological activity , protein subunit , receptor , biology , biochemistry , rna , gene , medicine , nursing
Sporolides A and B are novel polycyclic macrolides from the obligate marine actinomycetes, Salinispora tropica . The unique and novel structure of sporolides makes them interesting candidates for targeting diverse biological activities. Biological target prediction of sporolides was carried out using ligand‐based pharmacophore screening against known inhibitors and drugs. Validation of pharmacophore screening was carried out for the identified hits. New biological targets predicted for sporolides using this method were HIV ‐1 reverse transcriptase, adenosine A3 receptor, endothelin receptor ET ‐A, oxytocin receptor, voltage‐gated L‐type calcium channel α ‐1C subunit/calcium channel α /Δ subunit 1. Drug‐likeness properties were predicted for the selected compounds using QikProp module. Sporolides A and B showed maximum docking score with HIV ‐1 reverse transcriptase. Structural interaction fingerprints analysis indicated similar binding pattern of the sporolides with the HIV ‐1 reverse transcriptase. Sporolide B exhibited good inhibitory activity against HIV ‐1 reverse transcriptase in in vitro fluorescent assay.