Design, synthesis and pharmacological studies of some new quinoline Schiff bases and 2,5-(disubstituted-[1,3,4])-oxadiazoles

Abstract

Our aim with the present work was to design and synthesize quinoline Schiff bases and quinolinyloxadiazole hybrid molecules and assess them for in vitro antioxidant activities and antimicrobial properties against clinical isolates. Synthesized compounds were characterized using FT-IR, ¹H NMR, ¹³C NMR, mass spectra, and single crystal X-RD techniques. All compounds viz., 4a–g and 5a–g were efficiently synthesized in good yields in ranges of 76–84% and 80–85%, respectively. Newly synthesized compounds were screened for their antioxidant and antimicrobial potentials. Results were compared with standard antibacterial (amoxicillin and streptomycin) and antifungal (fluconazole) compounds which served as positive controls. Compounds 4b and 5g showed free radical scavenging activity of 26.55% (IC₅₀ value 288.38 μg mL⁻¹) and 27.22% (IC₅₀ value of 167.69 μg mL⁻¹), respectively. Compounds 4a, 4f, 5c, and 5e exhibited pronounced antimicrobial activity among all other synthesized compounds with zones of inhibition ranging between 10 ± 1 to 21 ± 1 mm and MIC 17 to 33.5 μg mL⁻¹. Molecular docking studies of the synthesized compounds revealed good binding via hydrogen bond interactions with key residues on active sites as well as neighboring residues with an active site of glucosamine-6-phosphate (G6P) synthase, the target protein which is essential for formation of bacterial or fungal cell walls, and indicating inhibition of G6P synthase. Among the synthesized compounds 4f, 5c, and 5b show the least binding energies of −9.31, −6.7 and −6.21 kcal mol⁻¹, respectively. Results from in silico investigation as well as in vitro antimicrobial studies suggest that the synthesized compounds may act as potential antimicrobial agents.