In silico evaluation of some newly synthesized quinoline derivatives as antimicrobial agents

Introduction: It is generally known that quinoline derivatives, particularly those that inhibit lipase and reductase, are strong antimicrobial agents. Several commercially available drugs, such as Bosutinib and Lenvatinib, are based on quinoline scaffolds.

Objective: The current research focused on the design and synthesis of novel quinoline derivatives, aiming to investigate their potential as multitarget enzyme receptor inhibitor and further evaluated for in-silico Antimicrobial Activity.

Methods: The named compounds were made primarily in three stages. Substituted Carboxylic acids of quinoline were synthesized using differently substituted isatins and acetophenones according to the Pfitzinger reaction. Benzotriazole-amines were synthesized in a second step, and the final compounds were obtained by reacting both of the intermediates in the presence of a base.

Results: Molecular docking studies were performed using the E. coli MsbA protein (PDB ID: 6BPP), which is in complex with lipopolysaccharide (LPS) and the inhibitor G092. Five designed compounds (5a–5e) were docked to evaluate their binding affinities. For screening, Lipinski’s Rule of Five and ADME (Absorption, Distribution, Metabolism, and Excretion) properties were analyzed using computational pharmacology tools alongside docking scores.

Conclusion: All synthesized compounds successfully passed the initial in silico screening. Among them, compounds 5a and 5d complied with Lipinski’s criteria and showed promising binding affinities. Compound 5a exhibited the strongest binding with a score of −8.7, while 5e also demonstrated notable affinity with a docking score of −8.3.

References:

1. Ali, M.R.; Kumar, S.; Afzal, O.; Shalmali, N.; Ali, W.; Sharma, M.;Bawa, S., Arch Pharm Chemistry in Life Sciences. 350, 2017, e1600313.