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

Abstract

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.

Low Blue Dose Photodynamic Therapy with Porphyrin-Iron Oxide Nanoparticles Complexes: In Vitro Study on Human Melanoma Cells

“…Molecules with estimated binding energy greater than −6 kcal/mol have no biological action on that target [53,54]. When TPPS interacts with Pro-caspase3, our results show that it has the lowest predicted binding energy −9.31 kcal/mol (Table 6).…”

Surface Chemical and Morphological Analysis of Chitosan/1,3-β-d-Glucan Polysaccharide Films Cross-Linked at 90 °C

“…Therefore, additional bands in chitosan/1,3-β- d -glucan spectra highlighted in pink were obtained on the basis of the second derivatives. In the ATR FT-IR spectrum ( Figure 1 B), a second derivative minimum at 2940 cm −1 is ascribed to C–H stretching [ 20 ]; 1635 cm −1 is ascribed to a β-sheet secondary structure in the amide I range [ 21 ], 1488 cm −1 is ascribed to aromatic C=C stretching, 1345 cm −1 is ascribed to OH deformation, 1173 cm −1 is ascribed to C–C ring and C–N stretching and OH and CH deformation, and 1126 cm −1 is ascribed to C–N ring stretching and CH deformation. In turn, 1063 cm −1 is assigned to CH 2 wagging from CH 3 groups, 1009 cm −1 is assigned to C–C ring, C–N ring and N–O stretching, 945 cm −1 is assigned to CH and OH deformation, 923 cm −1 is ascribed to CH 2 rocking, 843 cm −1 is assigned to C–N stretching and CH 2 rocking, and 820 cm −1 is ascribed to C–H, OH, and C=O deformation [ 20 ].…”

“…In the ATR FT-IR spectrum ( Figure 1 B), a second derivative minimum at 2940 cm −1 is ascribed to C–H stretching [ 20 ]; 1635 cm −1 is ascribed to a β-sheet secondary structure in the amide I range [ 21 ], 1488 cm −1 is ascribed to aromatic C=C stretching, 1345 cm −1 is ascribed to OH deformation, 1173 cm −1 is ascribed to C–C ring and C–N stretching and OH and CH deformation, and 1126 cm −1 is ascribed to C–N ring stretching and CH deformation. In turn, 1063 cm −1 is assigned to CH 2 wagging from CH 3 groups, 1009 cm −1 is assigned to C–C ring, C–N ring and N–O stretching, 945 cm −1 is assigned to CH and OH deformation, 923 cm −1 is ascribed to CH 2 rocking, 843 cm −1 is assigned to C–N stretching and CH 2 rocking, and 820 cm −1 is ascribed to C–H, OH, and C=O deformation [ 20 ]. In the Raman spectrum ( Figure 1 D), 496 488, and 659 cm −1 s derivative minima are attributed to C–C bending, 795 cm −1 is ascribed to CH 2 rocking, 850 cm −1 is assigned to =C–H wagging, 1172 cm −1 is assigned to CH 3 wagging, 1268 cm −1 is ascribed to CH 2 twisting, 1295 cm −1 is ascribed to =C–H bending, 1389 cm −1 is attributed to CH 3 asymmetrical deformation, and 1502 cm −1 is attributed to CH 2 deformation [ 22 ].…”

Network Pharmacology and Molecular Docking-Based Mechanism Study to Reveal the Protective Effect of Salvianolic Acid C in a Rat Model of Ischemic Stroke

“…Molecular docking is a computer-aided drug design method (Li T. et al, 2021). It can simulate the interaction between small molecule ligands and biological macromolecular receptors, and predict the binding mode and affinity between them (Udrea et al, 2021a;Udrea et al, 2021b), so as to screen the lead drugs that can bind to the target, and provide guidance for reasonably optimizing the molecular structure of drugs, which is of great significance for drug research and development.…”