The study of halogen effect on the reactivity of the serine-targeting covalent warheads.

IF 3.8 3区化学 Q2 CHEMISTRY, MULTIDISCIPLINARY Frontiers in Chemistry Pub Date : 2024-12-03 eCollection Date: 2024-01-01 DOI:10.3389/fchem.2024.1504453

Conghao Gai, Ya Zhang, Shihao Zhang, Xueyan Hu, Yun-Qing Song, Xiaoyu Zhuang, Xiaoyun Chai, Yan Zou, Guang-Bo Ge, Qingjie Zhao

引用次数: 0

Abstract

Halogens favorably contributes to the drug potency and metabolic stability via electrostatic interactions. Herein, the halogen effects on the reactivity of the halogenated 2,2,2-trifluoroacetophenones as serine-targeting covalent warheads were investigated. Our results showed that introducing halogen atoms, especially Cl or Br, into the phenyl scaffold would influence the electron density around the ring, which led to different time-dependent inhibition response to the target serine hydrolase (hCES1A). Co-crystallography analysis not only verified that halogenated molecules preferred to form covalent adducts, but also provided the conformational information for the design of covalent inhibitors targeting to hCES1A protein for the treatment of drug-induced acute enteritis.

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卤素对丝氨酸靶向共价战斗部反应性影响的研究。

卤素通过静电相互作用有利于药物效力和代谢稳定性。本文研究了卤素对卤代2,2,2-三氟苯乙酮作为丝氨酸靶向共价战斗部反应性的影响。我们的研究结果表明，在苯基支架中引入卤素原子，特别是Cl或Br，会影响环周围的电子密度，从而导致对目标丝氨酸水解酶（hCES1A）的不同时间依赖性抑制反应。共晶分析不仅证实了卤化分子倾向于形成共价加合物，而且为设计靶向hCES1A蛋白的共价抑制剂治疗药物性急性肠炎提供了构象信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Chemistry Chemistry-General Chemistry

CiteScore

8.50

自引率

3.60%

发文量

1540

审稿时长

12 weeks

期刊介绍： Frontiers in Chemistry is a high visiblity and quality journal, publishing rigorously peer-reviewed research across the chemical sciences. Field Chief Editor Steve Suib at the University of Connecticut is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to academics, industry leaders and the public worldwide. Chemistry is a branch of science that is linked to all other main fields of research. The omnipresence of Chemistry is apparent in our everyday lives from the electronic devices that we all use to communicate, to foods we eat, to our health and well-being, to the different forms of energy that we use. While there are many subtopics and specialties of Chemistry, the fundamental link in all these areas is how atoms, ions, and molecules come together and come apart in what some have come to call the “dance of life”. All specialty sections of Frontiers in Chemistry are open-access with the goal of publishing outstanding research publications, review articles, commentaries, and ideas about various aspects of Chemistry. The past forms of publication often have specific subdisciplines, most commonly of analytical, inorganic, organic and physical chemistries, but these days those lines and boxes are quite blurry and the silos of those disciplines appear to be eroding. Chemistry is important to both fundamental and applied areas of research and manufacturing, and indeed the outlines of academic versus industrial research are also often artificial. Collaborative research across all specialty areas of Chemistry is highly encouraged and supported as we move forward. These are exciting times and the field of Chemistry is an important and significant contributor to our collective knowledge.