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Design, Synthesis, and Biological Activity of Novel 1,3,5-Triazine–1,2,4-Triazine Hybrids as Cholinesterase Inhibitors

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Abstract

Fourteen 1,3,5-triazine–1,2,4-triazine hybrids were designed and synthesized. Their structures were confirmed by IR, NMR, and high-resolution mass spectra, as well as by single crystal X-ray diffraction. The cholinesterase inhibitory activities of the hybrids were assayed by Ellman’s method. Five of the fourteen hybrids inhibited acetylcholinesterase by more than 50% at a concentration of 50 μM. Only two hybrids inhibited butyrylcholinesterase by more than 50% at a concentration of 50 μM. Compound 5c possessed the best acetyl­cholinesterase and butyrylcholinesterase inhibitory activities with IC50 of 6.80±0.14 μM and 1.91±0.12 μM, respectively. Molecular docking showed that compound 5c interacted with both catalytic active site and peripheral anionic site of acetylcholinesterase.

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CONFLICT OF INTEREST

The authors declare no conflict of interest.

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Funding

This study has been supported by the graduate research and innovation projects of Jiangsu province (KYCX20-2895), Natural Science Foundation of Jiangsu province (BK20191470), and project funded by the priority academic program development of Jiangsu higher education institutions.

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Authors and Affiliations

  1. Jiangsu Key Laboratory of Marine Biotechnology, Jiangsu Ocean University/Jiangsu Key Laboratory of Marine Bioresources and environment, Jiangsu Ocean University, 222005, Lianyungang, China

    Chang-E. Dong, Rui Li, Zai-Xiu Pan, He Li, Jing-Jing Qian, Wei-Wei Liu, Zhi-Ling Cao & Da-Hua Shi

  2. School of Pharmacy, Jiangsu Ocean University, 222005, Lianyungang, China

    Chang-E. Dong, Rui Li, Zai-Xiu Pan, He Li, Jing-Jing Qian, Wei-Wei Liu, Zhi-Ling Cao & Da-Hua Shi

  3. Co-Innovation Center of Jiangsu Marine Bio-industry Technology, 222005, Lianyungang, China

    Wei-Wei Liu, Zhi-Ling Cao & Da-Hua Shi

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  1. Chang-E. Dong
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  2. Rui Li
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  4. He Li
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Correspondence to Zhi-Ling Cao or Da-Hua Shi.

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Dong, CE., Li, R., Pan, ZX. et al. Design, Synthesis, and Biological Activity of Novel 1,3,5-Triazine–1,2,4-Triazine Hybrids as Cholinesterase Inhibitors. Russ J Org Chem 59, 1610–1619 (2023). https://doi.org/10.1134/S1070428023090191

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