1,2,4三唑腙和磺胺类新衍生物的合成、表征、分子对接评价及抗血小板和抗凝血作用

Q1 Chemistry
Waseem Khalid, Amir Badshah, Arif-Ullah Khan, Humaira Nadeem, Sagheer Ahmed
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引用次数: 29

摘要

本研究合成了一系列新的1,2,4-三唑的腙类和磺胺类衍生物。首先用氯乙酸乙酯处理3个4-取代-5-(2-吡啶基)-1,2,4-三唑-3-硫酮ZE-1(a-c),得到相应的硫酯ZE-2(a-c),与水合肼反应得到相应的肼ZE-3(a-c)。将合成的肼与不同的醛和对甲苯磺酰氯缩合,分别得到目标腙衍生物ZE-4(a-c)和磺胺衍生物ZE-5(a-c)。所有合成的化合物均通过FTIR、1HNMR、13CNMR和元素分析数据进行了表征。此外,对新的腙类和磺胺类衍生物ZE-4(b-c)和ZE-5(a-b)的抗血小板和抗凝血活性进行了评价。ZE-4b、ZE-4c、ZE-5a和ZE-5b抑制花生四烯酸、二磷酸腺苷和胶原诱导的血小板聚集,其IC50值分别为40.1、785和10.01 (ZE-4b)、55.3、850.4和10 (ZE-4c)、121.6、956.8和30.1 (ZE-5a)、99.9、519和29.97 (ZE-5b)。其中以ZE-4c最有效,在30、100、300和1000µM时,PRT分别提高至84.2±1.88、142±3.51、205.6±5.37和300.2±3.48 s, BT分别延长至90.5±3.12、112.25±2.66、145.75±1.60 s (P < 0.05)
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Synthesis, characterization, molecular docking evaluation, antiplatelet and anticoagulant actions of 1,2,4 triazole hydrazone and sulphonamide novel derivatives.

Synthesis, characterization, molecular docking evaluation, antiplatelet and anticoagulant actions of 1,2,4 triazole hydrazone and sulphonamide novel derivatives.

Synthesis, characterization, molecular docking evaluation, antiplatelet and anticoagulant actions of 1,2,4 triazole hydrazone and sulphonamide novel derivatives.

Synthesis, characterization, molecular docking evaluation, antiplatelet and anticoagulant actions of 1,2,4 triazole hydrazone and sulphonamide novel derivatives.

In the present study, a series of new hydrazone and sulfonamide derivatives of 1,2,4-triazole were synthesized. Initially three 4-substituted-5-(2-pyridyl)-1,2,4-triazole-3-thiones ZE-1(a-c) were treated with ethyl chloroacetate to get the corresponding thioesters ZE-2(a-c), which were reacted with hydrazine hydrate to the respective hydrazides ZE-3(a-c). The synthesized hydrazides were condensed with different aldehydes and p-toluene sulfonylchloride to furnish the target hydrazone derivatives ZE-4(a-c) and sulfonamide derivatives ZE-5(a-c) respectively. All the synthesized compounds were characterized by FTIR, 1HNMR, 13CNMR and elemental analysis data. Furthermore, the new hydrazone and sulfonamide derivatives ZE-4(b-c) and ZE-5(a-b) were evaluated for their antiplatelet and anticoagulant activities. ZE-4b, ZE-4c, ZE-5a and ZE-5b inhibited arachidonic acid, adenosine diphosphate and collagen-induced platelets aggregation with IC50 values of 40.1, 785 and 10.01 (ZE-4b), 55.3, 850.4 and 10 (ZE-4c), 121.6, 956.8 and 30.1 (ZE-5a), 99.9, 519 and 29.97 (ZE-5b) respectively. Test compounds increased plasma recalcification time (PRT) and bleeding time (BT) with ZE-4c being found most effective, which at 30, 100, 300 and 1000 µM increased PRT to 84.2 ± 1.88, 142 ± 3.51, 205.6 ± 5.37 and 300.2 ± 3.48 s and prolonged BT to 90.5 ± 3.12, 112.25 ± 2.66, 145.75 ± 1.60 s (P < 0.001 vs. saline group) respectively. In silico docking approach was also applied to screen these compounds for their efficacy against selected drug targets of platelet aggregation and blood coagulation. Thus in silico, in vitro and in vivo investigations of ZE-4b, ZE-4c, ZE-5a and ZE-5b prove their antiplatelet and anticoagulant potential and can be used as lead molecules for further development.

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来源期刊
Chemistry Central Journal
Chemistry Central Journal 化学-化学综合
CiteScore
4.40
自引率
0.00%
发文量
0
审稿时长
3.5 months
期刊介绍: BMC Chemistry is an open access, peer reviewed journal that considers all articles in the broad field of chemistry, including research on fundamental concepts, new developments and the application of chemical sciences to broad range of research fields, industry, and other disciplines. It provides an inclusive platform for the dissemination and discussion of chemistry to aid the advancement of all areas of research. Sections: -Analytical Chemistry -Organic Chemistry -Environmental and Energy Chemistry -Agricultural and Food Chemistry -Inorganic Chemistry -Medicinal Chemistry -Physical Chemistry -Materials and Macromolecular Chemistry -Green and Sustainable Chemistry
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