Quinazoline Derivatives Designed as Efflux Pump Inhibitors: Molecular Modeling and Spectroscopic Studies

Molecules

Ana-Maria Udrea¹  Andra Dinache¹  Jean-Marie Pagès²  RuxandraAngela Pirvulescu³ 

[1] Laser Department, National Institute for Laser, Plasma and Radiation Physics, 077125 Magurele, Ilfov, Romania;UMR-MD1, U1261, Aix-Marseille Univ, INSERM, SSA, MCT, 13385 Marseille, France;University of Medicine and Pharmacy Carol Davila, 020022 Bucharest, Romania;

关键词: multidrug resistance;    MDR;    efflux pump inhibitor;    AcrAB-TolC pump;    quinazoline;    molecular docking;   

DOI  :  10.3390/molecules26082374

来源: DOAJ

【 摘 要 】

Multidrug resistance of bacteria is a worrying concern in the therapeutic field and an alternative method to combat it is designing new efflux pump inhibitors (EPIs). This article presents a molecular study of two quinazoline derivatives, labelled BG1189 and BG1190, proposed as EPIs. In silico approach investigates the pharmacodynamic and pharmacokinetic profile of BG1189 and BG1190 quinazolines. Molecular docking and predicted ADMET features suggest that BG1189 and BG1190 may represent attractive candidates as antimicrobial drugs. UV-Vis absorption spectroscopy was employed to study the time stability of quinazoline solutions in water or in dimethyl sulfoxide (DMSO), in constant environmental conditions, and to determine the influence of usual storage temperature, normal room lighting and laser radiation (photostability) on samples stability. The effects of irradiation on BG1189 and BG1190 molecules were also assessed through Fourier-transform infrared (FTIR) spectroscopy. FTIR spectra showed that laser radiation breaks some chemical bonds affecting the substituents and the quinazoline radical of the compounds.

【 授权许可】

Unknown