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Chinese Journal of Organic Chemistry >

2020 , Vol. 40 >Issue 2: 432 - 439

DOI: https://doi.org/10.6023/cjoc201907020

Synthesis of Amide Thioether Bridged 1,3-Selenazole and 1,2,4-Triazole Derivatives and Their Inhibitory Activity against Cell Division Cycle Phosphatase B (Cdc25B)

  • Zhang Chenglu ,
  • Wang Huayu ,
  • Yu Xiangkun ,
  • Yang Jingyi ,
  • Li Chuanyin ,
  • Gong Rongqin ,
  • Song Fulu ,
  • Sun Yuedong
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  • School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029

Received date: 2019-07-14

  Revised date: 2019-09-27

  Online published: 2019-10-12

Supported by

Project supported by the Science and Technology Research Program of Liaoning Provincial Department of Education (No. 2009A426).

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Abstract

The cell division cycle 25 phosphatase B (Cdc25B) is involved in carcinogenic transformation and is a potential drug target for anticancer therapy. In order to screen Cdc25B inhibitors, 1,3-selenazole was selected as the core block, and 1,2,4-triazole Schiff base was bridged into 2-(1,2,4-triazol-3-yl)thio-N-(4-phenyl-1,3-selenazolyl-2-yl)acetamide (TATS) by the amide thioether bond. The molecular docking simulation of TATS1 with Cdc25B was first performed to identify the rationality of the core function of 1,3-selenazole. The results show that 1,3-selenazole can be tightly embedded in the Cdc25B structure and perform N-H…PI non-bond weak interaction with the important catalytic site Arg492, which indicates that 1,3-selenazole plays a central role. The amide carbonyl oxygen atom forms a hydrogen bond with Arg492 and Arg488, indicating that the introduction of the amide thioether bond is reasonable. Based on the theoretical docking study, thirteen new target compounds TATS1~TATS13 were designed and synthesized through modification in two regions of 1,2,4-triazole Schiff base. The inhibition against Cdc25B of target molecules and important intermediates was tested respectively. As a result, the inhibitory activities of the intermediates are not good, 12 target compounds have better biological activity than the positive reference substance Na3VO4, the modifications of two regions of 1,2,4-triazole also have a significant effect, which suggests that these compounds are expected to be a potential inhibitor of Cdc25B.

Key words： 1,3-selenazole; 1,2,4-triazole Schiff base; molecular docking simulation; Cdc25B inhibitor

Cite this article

Zhang Chenglu , Wang Huayu , Yu Xiangkun , Yang Jingyi , Li Chuanyin , Gong Rongqin , Song Fulu , Sun Yuedong . Synthesis of Amide Thioether Bridged 1,3-Selenazole and 1,2,4-Triazole Derivatives and Their Inhibitory Activity against Cell Division Cycle Phosphatase B (Cdc25B)[J]. Chinese Journal of Organic Chemistry, 2020 , 40(2) : 432 -439 . DOI: 10.6023/cjoc201907020

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