In-silico molecular docking, ADMET and DFT evaluation of piperidin-4-one furoic hydrazone derivatives as antimicrobial, antioxidant and anticancer agents

A series of N'-(2,6-diarylpiperidin-4-ylidene)furan-2-carbohydrazide were synthesized by incorporating hydrazide group in piperidine moiety and characterized by IR, 1H, 13C NMR and Mass spectral techniques. The synthesized carbohydrazones were validated for their antioxidant, anticancer and antimicrobial studies. Compounds 6c and 6d with methoxy substituents disclosed better free radical scavenging activity than the other substituents. On the other hand, compounds bearing chloro substituents 6b, 6e and 6f exhibited enhanced activity in anticancer and antimicrobial assessments. To validate the experimental results, molecular docking simulations were carried out and the findings demonstrated minimum binding energy for compound 6b against the target protein 3E47. The In-silico ADMET profile evidenced optimal oral bioavailability data for these compounds. The molecular structure of 6b was evaluated by DFT calculations in B3LYP/6-31 + G(d,p) basis set, optimized parameters like dihedral angle, bond angle and bond length were calculated. To further comprehend the reactive sites of 6b, the HOMO-LUMO energy gap, molecular electrostatic potential and Mulliken charges were scrutinized. According to experimental and theoretical investigations, compound 6b displayed promising anticancer efficacy against the human cervical cancer HeLa cell line.