Effects of Salinispora derived metabolites against multidrug resistance, an in-silico study

Background: Multidrug resistance (MDR) is known to defeat most chemotherapies as one of the main anticancer strategies. The role of overexpression/overactivation of 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. Methods: In this study, the potential of Salinispora derived metabolites as inhibitor of ATP-binding cassette (ABC) transports have been investigated using in-silico approaches. Towards this end, physicochemical, pharmacokinetic and drug likeness of the 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 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.