Abstract
Two series of triazole derivatives were designed and synthesized as potential anticancer agents. A series of eighteen novel 1,2,3-triazole derivatives were synthesized through copper catalyzed click reaction. The compounds were evaluated for their cytotoxicity activity against HepG2, HeLa cell and HEK293 cell lines using MTT assay. The results showed that compounds 10 and 11 were the most potent compounds against HepG2 cell with IC50 values 9.6 and 13.3 μM, respectively. Additionally, the compounds 10 and 11 were the most potent compounds against HeLa cell with IC50 values 5.7 and 5.8 μM, respectively. The results of tubulin polymerization assay demonstrated that lead compound 2 and compound 10 could inhibit in vitro tubulin polymerization. In addition, a mechanism study displayed that 10 blocked cell cycle arrest at G2/M phase. Furthermore, a molecular docking study demonstrated that 10 can bind to the colchicine site of tubulin and form hydrogen bonds in the active site of β-tubulin. In summary, our study recommends a promising isoquinoline-triazole scaffold for further development as more efficient microtubule polymerization inhibitors in the field of cancer treatment.
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Acknowledgements
The authors gratefully acknowledge Thammasat University Research Unit in Drug, Health Product Development and Application (Project ID. 6305001), Thammasat University and this research was financially supported by the faculty of Pharmacy, Thammasat University (research project grant Pharm TU-S 1/2018). The authors wish to express their gratitude to Associate Professor Dr. Boon-ek Yingyongnarongkul, Faculty of Science, Ramkhamhaeng University (Thailand) for his facility support and Dr. Chutima Thepparit, Institute of Molecular Biosciences, Mahidol University for her valuable recommendation. Some equipment of structure characterization was supported by Faculty of Pharmacy, Thammasat University (Thailand).
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ST participated in design of study, provided the main synthesized compounds, elucidated structure of all compounds including interpret data and carried out the main biological experiment, CM carried out the main computer study and draft the manuscript in molecular docking study, RK and WS assisted in some synthesis and biological study, RA participated in partial biological experiment and OV helped to interpret the data and gave comment in experiment and manuscript.
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Theeramunkong, S., Maicheen, C., Krongsil, R. et al. Synthesis and in vitro biological evaluation of (iso)quinoline-1,2,3-triazole derivatives as anticancer agents. Chem. Pap. 76, 3971–3985 (2022). https://doi.org/10.1007/s11696-022-02140-0
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DOI: https://doi.org/10.1007/s11696-022-02140-0