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2-(N-((2'-(2H-四唑-5-基)-[1,1'-联苯]-4-基)-甲基)戊酰胺基)-3-甲基丁酸衍生物的合成、表征和生物评价。

Synthesis, Characterization, and Biological Evaluation of 2-(N-((2'-(2H-tetrazole-5-yl)-[1,1'-biphenyl]-4yl)-methyl)-pentanamido)-3-methyl Butanoic Acid Derivatives.

机构信息

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.

Faculty of Pharmacy, Universiti Teknologi, MARA Cawangan Selangor Kampus Puncak Alam, Bandar Puncak Alam 42300, Selangor, Malaysia.

出版信息

Molecules. 2023 Feb 16;28(4):1908. doi: 10.3390/molecules28041908.

Abstract

This study aimed to evaluate 2-(N-((2'-(2H-tetrazole-5-yl)-[1,1'-biphenyl]-4yl)-methyl)-pentanamido)-3-methyl butanoic acid-based ester derivatives as a new class of angiotensin-II receptor antagonists. For this purpose, a series of compounds were synthesized using a variety of phenols. Their chemical characterization was established by FTIR, HNMR, and CNMR techniques. The biological activities including antioxidant potentials using the DPPH assay, the antihypertensive assay, the urease enzyme inhibition assay, and the antibacterial assay using agar well diffusion methods were performed. All the new compounds showed significant free radical scavenging potentials more than the parent drug while retaining antihypertensive potentials along with urease inhibition properties. However, the AV2 test compound was found to be the most potent against hypertension. Most of the synthesized analogs showed urease inhibitory actions. Molecular docking studies were performed for all the active analogs to decode the binding detail of the ligands with receptors of the enzyme's active site.

摘要

本研究旨在评估 2-(N-((2'-(2H-四唑-5-基)-[1,1'-联苯]-4-基)-甲基)-戊酰胺基)-3-甲基丁酸酯衍生物作为一类新型血管紧张素 II 受体拮抗剂。为此,使用各种酚类合成了一系列化合物。通过傅里叶变换红外光谱(FTIR)、氢核磁共振(HNMR)和碳核磁共振(CNMR)技术确定了它们的化学特征。采用 DPPH 法测定抗氧化活性、测定抗高血压活性、测定脲酶抑制活性以及琼脂孔扩散法测定抗菌活性等方法进行了生物活性评价。所有新化合物均显示出比母体药物更强的自由基清除潜力,同时保持抗高血压潜力和脲酶抑制特性。然而,AV2 测试化合物被发现对高血压最有效。大多数合成的类似物具有脲酶抑制作用。对所有活性类似物进行了分子对接研究,以解析配体与酶活性部位受体的结合细节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58eb/9959676/4d13210aaeb6/molecules-28-01908-g001.jpg

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