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

Palwinder Singh, Jatinder Kaur, Bhawna Yadav, Sneha Sudha Komath

Journal: Bioorganic & medicinal chemistry 2010;18(12):4212-23

PMID: 20576574

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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.

Address: Department of Chemistry, Guru Nanak Dev University, Amritsar 143 005, India. [email protected]

DOI: 10.1016/j.bmc.2010.05.003

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MeSH Terms: ATP Binding Cassette Transporter, Subfamily B, Acridines, Acridones, Adenosine Triphosphate, Antifungal Agents, Binding Sites, Candida albicans, Computer Simulation, Drug Resistance, Multiple, Fungal, Magnesium, Spectrophotometry, Ultraviolet