Virtual and experimental high throughput screening of substituted hydrazones on ?-Tubulin polymerization
No Thumbnail Available
Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
Academic Press Inc.
Abstract
Microtubule targeting agents that disrupt the dynamic functioning of the mitotic spindle are some of the best chemotherapeutic agents. Interruption of microtubule dynamics through polymerization or depolymerization causes cell arrest leading to apoptosis. We report a novel class of aroylhydrazones with anticancer properties. Tubulin inhibition studies were performed using both computational and biological methods. Docking and pharmacophore mapping showed efficient binding between the ligands and the protein. Tubulin inhibition assay showed the aroylhydrazones to be inhibitors of tubulin polymerization. DFT studies explains the geometrical and electronic properties of the compounds. Furthermore, anticancer studies using lung and liver cancer cell lines gave low IC<inf>50</inf> values with the methyl substituted hydrazone MH-2 being the most potent. (IC<inf>50</inf> of 0.0896 and 0.1040 µM respectively). The methyl group is responsible for the effective binding to the protein. Thus, a new class of tubulin binding agents have been identified as potential agents in cancer therapy. © 2021 Elsevier Inc.
Description
Keywords
antineoplastic agent, beta tubulin, hydrazone derivative, methyl group, n' (4 (bis(2 chloroethyl)amino)benzylidene) 4 bromobenzohydrazide, n' (4 (bis(2 chloroethyl)amino)benzylidene) 4 chloro benzohydrazide, n' (4 (bis(2 chloroethyl)amino)benzylidene) 4 methyl benzhydrazide, n' (4 (bis(2 chloroethyl)amino)benzylidene) benzhydrazide, unclassified drug, tubulin, tubulin modulator, A-549 cell line, Article, biological activity, cancer cell line, cancer chemotherapy, carbon nuclear magnetic resonance, cheminformatics, controlled study, crystal structure, density functional theory, dose response, drug screening, drug synthesis, drug targeting, Fourier transform infrared spectroscopy, geometry, Hep-G2 cell line, high throughput screening, human, human cell, hydrogen bond, IC50, in vitro study, liver cancer, lung cancer, microtubule assembly, molecular docking, molecular interaction, pharmacophore, proton nuclear magnetic resonance, quantum mechanics, tubulin polymerization assay, ultraviolet visible spectrophotometry, virtual reality, X ray crystallography, X ray diffraction, cell proliferation, cell survival, chemical structure, chemistry, drug effect, metabolism, polymerization, structure activity relation, tumor cell line, Antineoplastic Agents, Cell Line, Tumor, Cell Proliferation, Cell Survival, Density Functional Theory, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, High-Throughput Screening Assays, Humans, Hydrazones, Molecular Docking Simulation, Molecular Structure, Polymerization, Structure-Activity Relationship, Tubulin, Tubulin Modulators
Citation
Bioorganic Chemistry, 2021, 114, , pp. -