Synthesis, bioinformatics and biological evaluation of novel pyridine based on 8-hydroxyquinoline derivatives as antibacterial agents: DFT, molecular docking and ADME/T studies

Abstract

• Synthesis of new compounds based on 8-hydroxyquinoline and their characterization by FT-IR, 1 H NMR, 13 C NMR and elemental analyses. • The antibacterial activity of all the compounds was carried out for five Gram-positive and Gram-negative strains. • The minimum inhibitory concentrations (MICs) of active compounds were calculated and discussed. • The chemical and biological activities of 8-Hydroxyquinoline derivatives were compared with theoretical methods (DFT, molecular docking, ADME/T). The present study aims to first explore the relationship between the chemical structure of the organic compounds (pyridine based on 8-hydroxyquinoline) and the antibacterial activities, as well as the impact of substituent effects on their antibacterial properties. These compounds were synthesized by efficient methods, and their structures confirmed by the spectral methods (IR, 1 H NMR, 13 C NMR and elemental analysis). The antibacterial activities of synthesized the compounds were checked with five Gram-positive and Gram-negative strains such as Enterobacter cloacae (ATCC29893),Escherichia coli (ATCC35218), Klebsiella pneumoniae (ATCC13883), Staphylococcus aureus ( ATCC29213 ) and Acinetobacter baumannii (ATCC19606) . The results of the antibacterial activities of four synthesized compounds were compared with three standard antibiotics [ Penicillin G, Erythromycin and Norfloxacin ( quinoline type)]. The minimum inhibitory concentrations (MICs) of active compounds were calculated and discussed. The chemical and biological activities of hydroxyquinoline derivatives were compared with theoretical methods. The chemical activities of hydroxyquinoline derivatives were contrasted with the important quantum chemical parameters using the HF/6–31++ g ( d, p ) basis sets. Besides, biological activities of hydroxyquinoline derivatives against cancer proteins that are respectively protein of the BRCT repeat region of breast cancer that is ID: 1JNX, crystal structure of liver cancer protein that is ID: 3WZE, and crystal structure of lung cancer protein that is ID: 5ZMA, were compared. ADME/T (Adsorption, Distribution, Metabolism, Excretion, and Toxicity) analysis was studied for molecules with high biological activity to become efficient drugs in the future.