title: 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.
abstract: 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.
authors.affiliation: Department of Bioinformatics, School of Bioengineering, Faculty of Engineering & Technology, SRM University, Kattankulathur, 603203, TamilNadu, India.
authors.forename: Kesavan
authors.initials: K
authors.lastname: Dineshkumar
authors.forename: Vasudevan
authors.initials: V
authors.lastname: Aparna
authors.forename: Kantilal Z
authors.initials: KZ
authors.lastname: Madhuri
authors.forename: Waheeta
authors.initials: W
authors.lastname: Hopper
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008024:Ligands; D018942:Macrolides / Q000737:chemistry* / Q000494:pharmacology; D008848:Micromonosporaceae / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D013816:Thermodynamics
chemical_list: D008024:Ligands; D018942:Macrolides; D018894:Reverse Transcriptase Inhibitors; C509191:sporolide A; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
keywords: HIV-1 reverse transcriptase; QikProp; Salinispora tropica; antiviral; induced fit docking; pharmacophore; sporolides A and B