Saima Daud , Obaid‐ur‐Rahman Abid , Malik Saadullah , M. Fakhar-e-Alam , Simone Carradori , Asma Sardar , Basit Niaz , M. Atif , Susi Zara , Muhammad Rashad
{"title":"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","authors":"Saima Daud , Obaid‐ur‐Rahman Abid , Malik Saadullah , M. Fakhar-e-Alam , Simone Carradori , Asma Sardar , Basit Niaz , M. Atif , Susi Zara , Muhammad Rashad","doi":"10.1016/j.jscs.2024.101905","DOIUrl":null,"url":null,"abstract":"<div><p>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 <sup>1</sup>H NMR, <sup>13</sup>C NMR and HRMS (EI). Biological evaluation (IC<sub>50</sub>) identified several derivatives <em>i.e.,</em> <strong>7a</strong> (urease = 17.37 ± 1.37 µM, α-glucosidase = 44.1 ± 1.15 µM), <strong>7j</strong>, (urease = 16.61 ± 1.37 µM, α-glucosidase = 81.2 ± 1.33 µM), <strong>7o</strong>, (urease = 18.63 ± 1.27 µM, α-glucosidase = 70.3 ± 1.14 µM), <strong>7r</strong> (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. <em>In silico</em> 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 <em>in vitro</em> research.</p></div>","PeriodicalId":16974,"journal":{"name":"Journal of Saudi Chemical Society","volume":"28 5","pages":"Article 101905"},"PeriodicalIF":5.8000,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1319610324001005/pdfft?md5=952b67fae9df2f4ffe01394e8a08bf6d&pid=1-s2.0-S1319610324001005-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Isatin-based ibuprofen and mefenamic acid Schiff base derivatives as dual inhibitors against urease and α–glucosidase: In vitro, in silico and cytotoxicity studies\",\"authors\":\"Saima Daud , Obaid‐ur‐Rahman Abid , Malik Saadullah , M. Fakhar-e-Alam , Simone Carradori , Asma Sardar , Basit Niaz , M. Atif , Susi Zara , Muhammad Rashad\",\"doi\":\"10.1016/j.jscs.2024.101905\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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 <sup>1</sup>H NMR, <sup>13</sup>C NMR and HRMS (EI). Biological evaluation (IC<sub>50</sub>) identified several derivatives <em>i.e.,</em> <strong>7a</strong> (urease = 17.37 ± 1.37 µM, α-glucosidase = 44.1 ± 1.15 µM), <strong>7j</strong>, (urease = 16.61 ± 1.37 µM, α-glucosidase = 81.2 ± 1.33 µM), <strong>7o</strong>, (urease = 18.63 ± 1.27 µM, α-glucosidase = 70.3 ± 1.14 µM), <strong>7r</strong> (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. 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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.
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.