Inhibitory Effects of Salinispora-derived Metabolites Against Multidrug Resistance: An In-silico Study

Abstract

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.