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

• Main Authors: Ana-Maria Udrea, Andra Dinache, Jean-Marie Pagès, Ruxandra Angela Pirvulescu
• Format: Article
• Language: English
• Published: MDPI AG 2021-04-01
• Series: Molecules
• Subjects: multidrug resistance; MDR; efflux pump inhibitor; AcrAB-TolC pump; quinazoline; molecular docking
• Online Access: https://www.mdpi.com/1420-3049/26/8/2374

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. <i>In silico</i> 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.