Open AccessInhibitory Effects of Salinispora-derived Metabolites Against Multidrug Resistance: An In-silico Study
Author(s) -
Morteza Ghandadi
Publication year - 2021
Publication title -
pharmaceutical and biomedical research
Language(s) - English
Resource type - Journals
eISSN - 2423-4494
pISSN - 2423-4486
DOI - 10.18502/pbr.v7i1.7354
Subject(s) - in silico , atp binding cassette transporter , multiple drug resistance , in vivo , p glycoprotein , pharmacology , transporter , chemistry , abcg2 , in vitro , docking (animal) , efflux , drug resistance , drug , pharmacokinetics , computational biology , biochemistry , biology , gene , microbiology and biotechnology , medicine , antibiotics , nursing
Background: Multi Drug Resistance (MDR) is known to defeat most chemotherapies as one of the main anticancer strategies. The role of overexpression or overactivation of ATPBinding Cassette (ABC) transporters, especially P-glycoprotein (P-gp), in the development of chemotherapy has long been demonstrated. Salinispora is a marine actinomycete genus known for the production of novel bioactive metabolites.
Objectives: In this study, the potential of Salinispora derived metabolites as inhibitor of ATPbinding cassette (ABC) transports have been investigated using in-silico approaches.
Methods: Physicochemical, pharmacokinetic and drug likeness of the Salinispora derived metabolites have been analyzed using SwissADME server. This was accompanied by the employment of docking strategy to evaluate anti-MDR potential of the metabolites using P-gp, Breast Cancer Resistance Protein (BCRP) and Multidrug Resistance Protein 1 (MRP-1) as target proteins.
Results: Nineteen metabolites were found to have demonstrated appropriate physicochemical, pharmacokinetic, and drug-likeness properties and were involved in the docking studies. Based on docking studies, saliniquinones, cyclomarazine, and cyanosporoside A demonstrated ABC transporters inhibitory potential.
Conclusion: Our results suggest that further in vivo and in vitro studies on anti-MDR effects of Salinispora-derived metabolites are warranted.