Synthesis, evaluation, and computational chemistry of novel selenenyl sulfides as 3C protease inhibitors with strong cell-based antiviral activity

Jin-Yin Tang; Shengwang Dai; Xiaofang Wang; Mengting Zhang; Jin-Rui Shi; Yong-Xuan Hong; Zhi-Juan Sun; Huan-Qin Dai; Jian-Guo Wang

Arabian Journal of Chemistry (Apr 2024)

Synthesis, evaluation, and computational chemistry of novel selenenyl sulfides as 3C protease inhibitors with strong cell-based antiviral activity

Jin-Yin Tang,
Shengwang Dai,
Xiaofang Wang,
Mengting Zhang,
Jin-Rui Shi,
Yong-Xuan Hong,
Zhi-Juan Sun,
Huan-Qin Dai,
Jian-Guo Wang

Affiliations

Jin-Yin Tang: State-Key Laboratory and Research Institute of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, National Engineering Research Center of Pesticide, College of Chemistry, Nankai University, Tianjin 300071, China
Shengwang Dai: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
Xiaofang Wang: Newish Biological R&D Center, Beijing 100176, China
Mengting Zhang: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
Jin-Rui Shi: State-Key Laboratory and Research Institute of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, National Engineering Research Center of Pesticide, College of Chemistry, Nankai University, Tianjin 300071, China
Yong-Xuan Hong: State-Key Laboratory and Research Institute of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, National Engineering Research Center of Pesticide, College of Chemistry, Nankai University, Tianjin 300071, China
Zhi-Juan Sun: Newish Biological R&D Center, Beijing 100176, China
Huan-Qin Dai: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 100049, China; Corresponding authors at: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China (H.Q. Dai).
Jian-Guo Wang: State-Key Laboratory and Research Institute of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, National Engineering Research Center of Pesticide, College of Chemistry, Nankai University, Tianjin 300071, China; Corresponding authors at: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China (H.Q. Dai).

Journal volume & issue: Vol. 17, no. 4
p. 105713

Abstract

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The 3C protease (3Cpro) is an important enzyme for developing therapeutic medicines against some severe viral infections. In order to discover new classes of antiviral agents, 42 novel selenenyl sulfides were prepared and characterized by 1H NMR, 13C NMR, 77Se NMR and HRMS. The target compounds demonstrated promising inhibitions against 3Cpro from either enterovirus 71 (EV71) or coxsackievirus B3 (CVB3), as well as desirable cell-based antiviral activity against these viruses. Among them, 11f displayed the most potent IC50 value of 0.28 ± 0.05 μM against EV71-3Cpro, and the strongest IC50 value of 0.72 ± 0.15 μM against CVB3, with a selectivity index of 51.5 against Hela cell, superior to the control drug rupintrivir. In addition, molecular docking was undertaken to predict a possible binding mode for compound 11f, and a comparative molecular field analysis (CoMFA) model was subsequently generated to understand the structure-activity relationships. Overall, the present research has provided some new insights to design a distinct family of antiviral compounds.

Published in Arabian Journal of Chemistry

ISSN: 1878-5352 (Print)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Chemistry
Website: http://www.journals.elsevier.com/arabian-journal-of-chemistry/

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