Affiliation:
1. Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, India-835215, India
Abstract
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.
Publisher
World Scientific Pub Co Pte Ltd
Subject
Computational Theory and Mathematics,Physical and Theoretical Chemistry,Computer Science Applications