Targeting efflux pumps—In vitro investigations with acridone derivatives and identification of a lead molecule for MDR modulation

Abstract

To search multi drug resistance modulators, acridones carrying hydroxyl amine substituent at N-10 and COOH/Cl at C-4 were investigated for their interactions with the three components of efflux pump viz. P-gp, ATP, and Mg 2+. Experimental and theoretical results indicated that the compounds with COOH group at C-4 interact with P-gp and Mg 2+ while other set of compounds with Cl at C-4 interact with ATP and Mg 2+. Spot assay and R6G influx/efflux assay of compound 3 using Candida albicans showed decrease in the fungal growth and efflux of R6G, respectively, in presence of compound 3 suggesting the suitability of this compound for MDR modulation.