Design, synthesis and molecular docking study of thiophenyl hydrazone derivatives as tubulin polymerization inhibitors

Abstract

A series of thiophene derivatives substituted at 2, 3 and 5 positions were designed and synthesized using 2,3-disubstituted thiophene aldehyde and alcohol as key building blocks. Invitro cytotoxicity assessed against PC-3, DU145 (prostate), A549 (lung), HT29, HCT116 (colon), MCF7, MDAMB231 (breast), B16F10 (melanoma) NCI (Colorectal) cancer cell lines by conducting (MTT) assay of thiophene derivatives. Most of these synthesized compounds showed anti-cancer activity, compound 5b showed good cytotoxicity with IC₅₀ = 2.61 ± 0.34 µM on HT29 cell line. Also, the key property of cell migration was observed while treating cells with 5b. The Cell cycle arrest at G2/M phase was observed by 5b on HT29 cell line which inhibited tubulin polymerization with IC₅₀ value of 8.21 ± 0.30 μM. Moreover, binding pose with co-crystal ligand and interaction with colchicine binding site of 5b was established by molecular docking studies. Hence this scaffold can be developed as anti-cancer agents that target tubulin polymerization.

Graphical Abstract

Keywords:

• Annexin-V binding assay
• cytotoxicity analysis
• G2/M arrest
• Hydrazones
• molecular docking

Acknowledgements

We gratefully acknowledge Schrodinger LLC, New York for providing us the software. We wish to express our gratitude to Department of Chemistry, Osmania University for providing facilities to carry out the research work. One of the authors Vaeshnavi Kashetti would like to thank DST for providing Inspire Fellowship (IF180224). This research was made possible through grants from Council of Scientific and Industrial Research [02(0379)/19/EMR-II] and DST-PURSE-II (2017–2021).

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Supplementary information

Full experimental detail, 1H and 13 C NMR spectra etc material can be found in the “Supplementary information”.

Additional information

Funding

This work was supported by the Department of Science and Technology, Ministry of Science and Technology.