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Design, synthesis, and bioevaluation of novel oxoindolin-2-one derivatives incorporating 1-benzyl-1H-1,2,3-triazole


In our search for novel bioactive molecules, three series of indolin-2-one derivatives incorporating 1-benzyl-1H-1,2,3-triazole moiety were synthesized. The compounds were initially designed as acetylcholine esterase (AChE) inhibitors based on the structural feature of donepezil, a known AChE inhibitor which is currently used clinically to treat Alzheimer’s disease (AD). Two compounds 4g and 3a were found to be the most potent in inhibition of AChE with inhibition percentages of 51 and 50% when tested at the concentration of 100 μM. Docking assays were carried out in order to explain the structure–activity relationships of these compounds compared with Donepezil against AChE enzyme. In DPPH free radical-scavenging assay, most compounds showed only weak scavenging activity. Noteworthy, additional cytotoxic evaluation of the compounds against three human cancer cell lines (SW620, human colon cancer; PC3, prostate cancer; NCI-H23, lung cancer) revealed that five compounds, including 3c, 3e, 5c, 5e, and 5g, exhibited strong cytotoxicity (IC50 values in the range of 0.65–7.17 µM). Compound 5g was the most potent one with IC50 values as low as 0.65 μM, even more potent than adriamycin, a positive control. Thus, compound 5g would be promising for further development as an anticancer agent.

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We acknowledge the principal financial supports from the National Foundation for Science and Technology of Vietnam (NAFOSTED, Grant number 104.01-2018.301). The work was also partly supported by a grant funded by the Korean Government (NRF, Grant number 2017R1A5A2015541).

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Correspondence to Sang-Bae Han or Nguyen-Hai Nam.

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Lan, T.T., Anh, D.T., Hai, PT. et al. Design, synthesis, and bioevaluation of novel oxoindolin-2-one derivatives incorporating 1-benzyl-1H-1,2,3-triazole. Med Chem Res 29, 396–408 (2020).

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  • Acetylcholine esterase inhibitors
  • Oxoindolin-2-one
  • Cytotoxicity
  • Docking simulation