Synthesis of New Hydrazones Using a Biodegradable Catalyst, Their Biological Evaluations and Molecular Modeling Studies (Part-II)

Hydrazones typically have an azomethine ‘–NHN=CH group’ which is crucial for varieties of pharmacological activities. In this study, we have synthesized a set of 15 new hydrazones (5A–5O) of 2-((2,3-dihydro-1H-inden-4-yl)oxy)acetohydrazide, which were characterized with various spectroscopic methods. It was found that the compound 5H had significant bioactivities (Antioxidant: DPPH assay: 80.3% inhibition; at 100[Formula: see text][Formula: see text]g/mL concentration; Antibacterial: Minimum inhibitory concentration (MIC) of 6.25[Formula: see text][Formula: see text]g/mL against E. coli; Antimycobacterial, H37Rv Vaccine strain: MIC of 3.12[Formula: see text][Formula: see text]g/mL; Anticancer: Trypan Blue assay, MCF-7; IC[Formula: see text] values of 84.3[Formula: see text]mM). To understand the probable underlying antibacterial mechanisms, we examined all hydrazones against a common bacterial target (2,2-dialkylglycine decarboxylase, PDB ID: 1d7u) and pantothenate synthase from Mycobacteria (PDB ID: 3ivx) using molecular docking. Our molecular dynamics simulations for 100[Formula: see text]ns for both the complexes (5H:1d7u and 5H:3ivx) revealed significant stability of ligand–protein complex. Moreover, to correlate structural features with biological activity, we have developed statistically significant 5-parametric Quantitative Structure–Activity Relationships (QSAR) models. The pharmacophore hypothesis, AADHR_1 (5-point) signifies its importance for biological activities. Finally, we have examined the theoretical and pharmacokinetics and toxicity properties of all synthesized compounds.