Design, Synthesis, Antimicrobial and Antimalarial Evaluation of Quinoline Hydrazone Derivatives: Insight through DFT Analysis, Molecular Docking and ADMET Predictions

Antimicrobial and antimalarial resistance are the major global health threats and indicating to develop the novel targeted molecules to overcome the resistance problem. In this concern, in the present study, some quinoline hydrazone derivatives (6a‐6o) have been synthesised and evaluated as antimicrobial and antimalarial agents. Compound 6o was observed to be the most active and presented equipotent antibacterial activity (MIC = 6.25 µg/ml) as the standard drug Ofloxacin against E. coli and P. aeruginosa. Antimalarial activity showed that compound 6g exhibited maximum inhibitory action (IC50 = 0.56 µg/ml) and was significant in contrast to standard drugs Chloroquine (IC50 = 0.020 µg/ml) and Quinine (IC50 = 0.268 µg/ml) against P. falciparum. DFT analysis evaluated the chemical reactivity of molecular orbitals of the most active compounds 6g and 6o. Furthermore, molecular docking study showed that most active antimalarial (6g) and antimicrobial (6o) compounds exhibited potent interactions with targeted enzymes (Lactate dehydrogenase and Dihydrofolate reductase, respectively). In‐silico drug‐likeness parameters and ADMET study indicated that all the synthesized derivatives followed the acceptance criteria. The present study emphasized that compounds 6g (antimalarial) and 6o (antimicrobial) could be developed as novel inhibitors against lactate dehydrogenase and DHFR enzyme, respectively on the completion of drug discovery approaches.