Design, Synthesis and Evaluation of Substituted N-(3-Arylpropyl)-9,10-dihydro-9-oxoacridine-4-carboxamides as Potent MDR Reversal Agents in Cancer

• Published in: Chinese journal of chemistry 2011-03, Vol.29 (3), p.504-510
• Main Authors: Velingkar, V. S., Dandekar, V. D.
• Format: Article
• Language: English
• Subjects: 10-dihydro-9-oxo-acridine-4-carboxamides; Design; MDR reversal agents; N-(3-arylpropyl)-9; N‐(3‐arylpropyl)‐9,10‐dihydro‐9‐oxo‐acridine‐4‐carboxamides; pharmacophore; phase drug design software; structure elucidation; structure-activity relationships
• ISSN: 1001-604X; 1614-7065
• DOI: 10.1002/cjoc.201190113

A novel class of molecules with structure N‐(3‐arylpropyl)‐9,10‐dihydro‐9‐oxoacridine‐4‐carboxamides (20–29) were designed by generating a pharmacophore for potent MDR reversal activity using phase drug design software. The designed molecules were synthesized by a novel synthesis route and evaluated for their inhibitory effects on the transport activity of P‐glycoprotein (P‐gp) by standard Hoechst 33342 assay method. Based on the pIC50 values of ten title compounds screened, three compounds exhibited better activity as compared to Verapamil used as standard. A novel class of molecules with structure N‐(3‐arylpropyl)‐9,10‐dihydro‐9‐oxo‐acridine‐4‐carboxamides were designed by generating a pharmacophore for potent MDR reversal activity using phase drug design software. The designed molecules were synthesized by a novel synthesis route and evaluated for their inhibitory effects on the transport activity of P‐glycoprotein (P‐gp) by standard Hoechst 33342 assay method. Based on the pIC50 values of ten title compounds screened, three compounds exhibited better activity as compared to Verapamil used as standard.