基于异铂的布洛芬和甲灭酸席夫碱衍生物作为脲酶和α-葡萄糖苷酶的双重抑制剂:体外、硅学和细胞毒性研究

IF 5.8 2区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Journal of Saudi Chemical Society Pub Date : 2024-07-14 DOI:10.1016/j.jscs.2024.101905
Saima Daud , Obaid‐ur‐Rahman Abid , Malik Saadullah , M. Fakhar-e-Alam , Simone Carradori , Asma Sardar , Basit Niaz , M. Atif , Susi Zara , Muhammad Rashad
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引用次数: 0

摘要

α-葡萄糖苷酶和脲酶抑制剂已成为开发糖尿病和胃肠道疾病治疗药物的关键。本研究报告了一系列新的布洛芬和甲灭酸席夫碱衍生物,这些衍生物含有异汀,是 α-葡萄糖苷酶和脲酶的双重抑制剂。这些合成的衍生物(7a-r)通过 1H NMR、13C NMR 和 HRMS(EI)进行了结构表征。生物学评价(IC50)确定了几种衍生物,即7a(脲酶 = 17.37 ± 1.37 µM,α-葡萄糖苷酶 = 44.1 ± 1.15 µM)、7j(脲酶 = 16.61 ± 1.37 µM,α-葡萄糖苷酶 = 81.2 ± 1.33 µM)、7o(脲酶 = 18.63 ± 1.27 µM,α-葡萄糖苷酶 = 70.3 ± 1.14 µM)、7r(脲酶 = 11.36 ± 1.32 µM,α-葡萄糖苷酶 = 39.3 ± 1.17 µM),作为脲酶(硫脲 21.37 ± 1.76 µM)和α-葡萄糖苷酶(阿卡波糖 375.82 ± 1.76 µM)的双重抑制剂。对这些生物活性衍生物进行了针对单核细胞的细胞活力研究,结果表明它们具有良好的细胞相容性。此外,还进行了硅学分子对接研究,以预测新衍生物与目标酶的结合模式,结果与体外研究结果一致。
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Isatin-based ibuprofen and mefenamic acid Schiff base derivatives as dual inhibitors against urease and α–glucosidase: In vitro, in silico and cytotoxicity studies

α-Glucosidase and urease inhibitors have emerged as crucial for developing therapeutic drugs targeting diabetes and gastrointestinal disorders. This study reports on new series of ibuprofen and mefenamic acid Schiff base derivatives incorporating isatin as dual inhibitors of α-glucosidase and urease enzymes. These synthesized derivatives (7a-r) were structurally characterized by 1H NMR, 13C NMR and HRMS (EI). Biological evaluation (IC50) identified several derivatives i.e., 7a (urease = 17.37 ± 1.37 µM, α-glucosidase = 44.1 ± 1.15 µM), 7j, (urease = 16.61 ± 1.37 µM, α-glucosidase = 81.2 ± 1.33 µM), 7o, (urease = 18.63 ± 1.27 µM, α-glucosidase = 70.3 ± 1.14 µM), 7r (urease = 11.36 ± 1.32 µM, α-glucosidase = 39.3 ± 1.17 µM), as dual inhibitors of urease (thiourea 21.37 ± 1.76 µM) and α–glucosidase (acarbose 375.82 ± 1.76 µM) enzymes. These bioactive derivatives were explored for cell viability studies against mononuclear cells revealing a good cytocompatibility. In silico molecular docking studies were also conducted to predict the binding mode of new derivatives with target enzymes that were found consistent with the results of in vitro research.

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来源期刊
Journal of Saudi Chemical Society
Journal of Saudi Chemical Society CHEMISTRY, MULTIDISCIPLINARY-
CiteScore
8.90
自引率
1.80%
发文量
120
审稿时长
38 days
期刊介绍: Journal of Saudi Chemical Society is an English language, peer-reviewed scholarly publication in the area of chemistry. Journal of Saudi Chemical Society publishes original papers, reviews and short reports on, but not limited to: •Inorganic chemistry •Physical chemistry •Organic chemistry •Analytical chemistry Journal of Saudi Chemical Society is the official publication of the Saudi Chemical Society and is published by King Saud University in collaboration with Elsevier and is edited by an international group of eminent researchers.
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