Targeting efflux pumps-In vitro investigations with acridone derivatives and identification of a lead molecule for MDR modulation.
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.
Singh
Palwinder
P
Department of Chemistry, Guru Nanak Dev University, Amritsar 143 005, India. palwinder_singh_2000@yahoo.com
Kaur
Jatinder
J
Yadav
Bhawna
B
Komath
Sneha Sudha
SS
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000166:Acridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D054831:Acridones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D002176:Candida albicans / Q000187:drug effects; D003198:Computer Simulation; D026141:Drug Resistance, Multiple, Fungal / Q000187:drug effects*; D008274:Magnesium / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
D018435:ATP Binding Cassette Transporter, Subfamily B; D000166:Acridines; D054831:Acridones; D000935:Antifungal Agents; D000255:Adenosine Triphosphate; D008274:Magnesium