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含苯并噻唑的吡唑啉类化合物作为抗炎剂的合成与评价

Synthesis and evaluation of pyrazolines bearing benzothiazole as anti-inflammatory agents.

作者信息

Kharbanda Chetna, Alam Mohammad Sarwar, Hamid Hinna, Javed Kalim, Bano Sameena, Dhulap Abhijeet, Ali Yakub, Nazreen Syed, Haider Saqlain

机构信息

Department of Chemistry, Faculty of Science, Hamdard University, New Delhi 110 062, India.

Department of Chemistry, Faculty of Science, Hamdard University, New Delhi 110 062, India.

出版信息

Bioorg Med Chem. 2014 Nov 1;22(21):5804-12. doi: 10.1016/j.bmc.2014.09.028. Epub 2014 Sep 28.

Abstract

The present study aims at the synthesis of pyrazolines bearing benzothiazole and their evaluation as anti-inflammatory agents. The synthesized compounds were evaluated for their anti-inflammatory potential using carrageenan induced paw edema model. Two compounds 5a and 5d alleviated inflammation more than the standard drug celecoxib. Eight compounds 5 b, 5 c, 5 e, 5 g, 5 h, 6 b, 6 e and 6 f showed anti-inflammatory activity comparable to celecoxib. To understand the mode of action, COX-2 enzyme assay and TNF-α assay were carried out. All the active compounds were assessed for their cytotoxicity. The ulcerogenic risk evaluation was performed on the active compounds that were not found to be cytotoxic. Out of ten active compounds, two compounds (5 d and 6 f) were finally found to be the most potent anti-inflammatory agents attributing to the suppression of the COX-2 enzyme activity and TNF-α production without being either cytotoxic or ulcerogenic.

摘要

本研究旨在合成含苯并噻唑的吡唑啉及其作为抗炎剂的评估。使用角叉菜胶诱导的爪肿胀模型评估合成化合物的抗炎潜力。两种化合物5a和5d比标准药物塞来昔布更能减轻炎症。八种化合物5b、5c、5e、5g、5h、6b、6e和6f显示出与塞来昔布相当的抗炎活性。为了解作用模式,进行了COX-2酶测定和TNF-α测定。评估所有活性化合物的细胞毒性。对未发现具有细胞毒性的活性化合物进行致溃疡风险评估。在十种活性化合物中,最终发现两种化合物(5d和6f)是最有效的抗炎剂,归因于它们抑制COX-2酶活性和TNF-α产生,且既无细胞毒性也无致溃疡性。

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