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苯并咪唑药效团衍生物的合成、抗惊厥、抗糖尿病和 DNA 切割研究。

Derivatives of benzimidazole pharmacophore: synthesis, anticonvulsant, antidiabetic and DNA cleavage studies.

机构信息

P.G. Department of Studies in Chemistry, Karnatak University, Pavate Nagar, Dharwad-580 003, Karnataka, India.

出版信息

Eur J Med Chem. 2010 May;45(5):1753-9. doi: 10.1016/j.ejmech.2010.01.007. Epub 2010 Jan 14.

Abstract

In seeking broad spectrum pharmacological activities of benzimidazole derivatives, a group of 4-thiazolidinones 5(a-j) and 1,3,4-oxadiazoles 6(a-j) containing 2-mercapto benzimidazole moiety were synthesized and screened for in vivo anticonvulsant activity by Maximal Electroshock (MES) model and antidiabetic activity using Oral Glucose Tolerance Test (OGTT). Compounds (5c), (5d), (5g) and (5i) exhibited potent anticonvulsant results and (6c), (6d), (6h) and (6i) showed excellent antidiabetic activities and also pharmacophore derived from active molecules suggested that presence of -OH group was a common feature in all active compounds. In DNA cleavage studies, compound (5d) cleaved DNA completely as no trace of DNA was found. On the other hand, a sharp streak was found for compounds (5c), (6a) and (6d).

摘要

在寻求苯并咪唑衍生物的广谱药理活性时,我们合成了一组含有 2-巯基苯并咪唑部分的 4-噻唑烷酮 5(a-j)和 1,3,4-噁二唑 6(a-j),并通过最大电休克 (MES) 模型和口服葡萄糖耐量试验 (OGTT) 筛选其体内抗惊厥活性和抗糖尿病活性。化合物 (5c)、(5d)、(5g) 和 (5i) 表现出有效的抗惊厥作用,而 (6c)、(6d)、(6h) 和 (6i) 则表现出优异的抗糖尿病作用,并且基于活性分子推导的药效团表明,所有活性化合物都具有 -OH 基团。在 DNA 切割研究中,化合物 (5d) 完全切割了 DNA,因为没有发现 DNA 的痕迹。另一方面,化合物 (5c)、(6a) 和 (6d) 则出现了明显的条带。

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