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Synthesis and in vitro cytotoxic evaluation of novel \(N\)-(3,4,5-trimethoxyphenyl)pyridin-2(\(1H\))-one derivatives

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Abstract

A series of novel \(N\)-(3,4,5-trimethoxyphenyl)pyridin-2(\(1H\))-one derivatives were designed, synthesized, and evaluated for their in vitro cytotoxicity against human colon cancer cells HCT-116. The key steps involved consecutive Chan–Lam- and Buchwald–Hartwig couplings. Most of these C-6 substituted pyridone derivatives showed moderate antiproliferative activity. The preliminary SAR indicated that the conformationally restricted pyridones exhibited more potent cytotoxicity than the flexible counterparts. In addition, cell cycle analysis of the selected compounds 4b and e showed a G2/M arrest, suggesting a possible antitubulin mechanism for these novel pyridone derivatives.

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Acknowledgments

This work was supported by the Grants of The National Natural Science Foundation of China (Nos. 81172936 and 21102046) and Grants of The Fundamental Research Funds for the Central Universities. We also thank The Laboratory of Organic Functional Molecules, the Sino-French Institute of ECNU for support.

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Authors and Affiliations

  1. Department of Chemistry, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China

    Taijie Chen & Yu Luo

  2. Institute of Drug Discovery and Development, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China

    Wei Lu

  3. Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zu Chong Zhi Road, Shanghai, 201203, China

    Li Sheng, Jia Li & Youhong Hu

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  1. Taijie Chen
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  4. Jia Li
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Correspondence to Yu Luo or Wei Lu.

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Chen, T., Luo, Y., Sheng, L. et al. Synthesis and in vitro cytotoxic evaluation of novel \(N\)-(3,4,5-trimethoxyphenyl)pyridin-2(\(1H\))-one derivatives. Mol Divers 17, 435–444 (2013). https://doi.org/10.1007/s11030-013-9442-1

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