Design, synthesis, biological and in silico evaluation of coumarin-hydrazone derivatives as tubulin targeted antiproliferative agents

• Published in: Bioorganic chemistry 2019-10, Vol.91, p.103143, Article 103143
• Main Authors: Govindaiah, Pilli, Dumala, Naresh, Mattan, Irshad, Grover, Paramjit, Jaya Prakash, M.
• Format: Article
• Language: English
• Subjects: ADMET; Anticancer; Coumarin; Hydrazone; Lipinski’s rule; Molecular docking; Tubulin
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2019.103143

[Display omitted] •Syntheiszed different sets of coumarin based hydrazone derivatives.•All the compounds were characterised by FT-IR, NMR and ESI-MS spectroscopic methods.•Evaluated for antiproliferative activity against different cancer cell lines (A549, HeLa, SKNSH, and MCF7).•Tubulin polymerization inhibition assay was performed and compared with standard drug colchicine.•The tubulin polymerization inhibition assay results were validated with molecular docking simulation study with the tubulin protein retrieved from protein data bank (PDB ID: 4YJ3).•All the synthesized compounds molecular properties and pharmacokinetic properties were predicted by using some online servers and software’s. Coumarin-based different series of hydrazone derivatives were synthesized and evaluated for anticancer activity against four different human cancer cell lines. The activity of the compounds were compared with doxorubicin as a standard drug and all the compounds exhibited good to moderate cytotoxicity with IC50 values ranging from 6.07 to 60.45 µM against all the examined cancer cell lines. Based on the screening results, it was concluded that the compounds 12a and 18a were the most promising medicinal entities. In vitro tubulin polymerisation inhibition assay was performed for the compounds 12a and 18a and these two compounds displayed good potency when compared with colchicine as the standard drug. The interaction of these compounds with tubulin protein was also studied with the help of molecular docking technique using Discovery studio software. Furthermore, the molecular and ADMET properties of the compounds were computed with Osiris property software and PreADMET server. The compounds exhibited exciting in vitro and in silico results. Hence we propose that the compounds 12a and 18a could be developed as tubulin targeted potential antiproliferative agents.