{"title":"新型噁二唑衍生物的合成:DFT 计算、分子对接研究以及利用黑腹果蝇模型进行的体外和体内抗糖尿病活性评估","authors":"Govinda Anjanayya, Ramesh Gani, Avinash Kudva, Shrinivas Joshi, Murigendra Hiremath, Apsara Kavital, Karabasanagouda Timanagouda, Basavarajaiah Mathada, Mohammad Javeed, Raifa Aziz, Shamprasad Raghu","doi":"10.1007/s13738-024-03067-x","DOIUrl":null,"url":null,"abstract":"<div><p>Current antidiabetic medications have a plethora of harmful side effects, and most of the drugs do not contain 1,3,4-oxadiazole moiety. Therefore, research into the development of novel drugs which contain 1,3,4-oxadiazole moiety with fewer side effects is necessary. Novel fluorine-incorporated 1,3,4-oxadiazole derivatives <b>(1c–1n)</b> were synthesized, characterized, and evaluated for <i>α</i>-amylase and <i>α</i>-glucosidase enzyme inhibitor activity. An in vivo <i>Drosophila melanogaster</i> model and an in vitro system were used to investigate its antidiabetic properties, further, which were characterized by <sup>1</sup>HNMR, MASS, and FT-IR. Spectroscopic techniques and DFT are used to calculate more geometrically optimized molecule structures using the B3LYP technique. The compounds were tested against the <i>α</i>-glucosidase and <i>α</i>-amylase enzymes. Among different compounds tested, compounds <b>1i</b> (IC<sub>50</sub> = 54.83 µg/ml), <b>1k</b> (IC<sub>50</sub> = 64.95 µg/ml), 1<b>m</b> (IC<sub>50</sub> = 64.78 µg/ml), and <b>1n</b> (IC<sub>50</sub> = 66.30 µg/ml) showed significant <i>α</i>-amylase inhibitor efficacy compared to the acarbose (IC<sub>50</sub> = 35.17 µg/ml); compounds <b>1m</b> (IC<sub>50</sub> = 74.64 µg/ml) and <b>1i</b> (IC<sub>50</sub> = 60.35 µg/ml) exhibited significant <i>α</i>-glucosidase inhibitory action compared to acarbose <b>(</b>IC<sub>50</sub> = 46.06 µg/ml). The docking study exhibited that compound <b>1i</b> creates six hydrogen bonds and compound <b>1m</b> forms three hydrogen bonding contacts at the active site of the enzyme (PDBID:4w93). The obtained results are demonstrated that compounds <b>1i, 1m, 1n, and 1k</b> had greater antidiabetic activities and can be further taken into consideration for antidiabetic therapeutic interventions.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":676,"journal":{"name":"Journal of the Iranian Chemical Society","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis of novel oxadiazole derivatives: DFT calculations, molecular docking studies, and in vitro, in vivo evaluation of antidiabetic activity using Drosophila melanogaster model\",\"authors\":\"Govinda Anjanayya, Ramesh Gani, Avinash Kudva, Shrinivas Joshi, Murigendra Hiremath, Apsara Kavital, Karabasanagouda Timanagouda, Basavarajaiah Mathada, Mohammad Javeed, Raifa Aziz, Shamprasad Raghu\",\"doi\":\"10.1007/s13738-024-03067-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Current antidiabetic medications have a plethora of harmful side effects, and most of the drugs do not contain 1,3,4-oxadiazole moiety. Therefore, research into the development of novel drugs which contain 1,3,4-oxadiazole moiety with fewer side effects is necessary. Novel fluorine-incorporated 1,3,4-oxadiazole derivatives <b>(1c–1n)</b> were synthesized, characterized, and evaluated for <i>α</i>-amylase and <i>α</i>-glucosidase enzyme inhibitor activity. An in vivo <i>Drosophila melanogaster</i> model and an in vitro system were used to investigate its antidiabetic properties, further, which were characterized by <sup>1</sup>HNMR, MASS, and FT-IR. Spectroscopic techniques and DFT are used to calculate more geometrically optimized molecule structures using the B3LYP technique. The compounds were tested against the <i>α</i>-glucosidase and <i>α</i>-amylase enzymes. Among different compounds tested, compounds <b>1i</b> (IC<sub>50</sub> = 54.83 µg/ml), <b>1k</b> (IC<sub>50</sub> = 64.95 µg/ml), 1<b>m</b> (IC<sub>50</sub> = 64.78 µg/ml), and <b>1n</b> (IC<sub>50</sub> = 66.30 µg/ml) showed significant <i>α</i>-amylase inhibitor efficacy compared to the acarbose (IC<sub>50</sub> = 35.17 µg/ml); compounds <b>1m</b> (IC<sub>50</sub> = 74.64 µg/ml) and <b>1i</b> (IC<sub>50</sub> = 60.35 µg/ml) exhibited significant <i>α</i>-glucosidase inhibitory action compared to acarbose <b>(</b>IC<sub>50</sub> = 46.06 µg/ml). The docking study exhibited that compound <b>1i</b> creates six hydrogen bonds and compound <b>1m</b> forms three hydrogen bonding contacts at the active site of the enzyme (PDBID:4w93). The obtained results are demonstrated that compounds <b>1i, 1m, 1n, and 1k</b> had greater antidiabetic activities and can be further taken into consideration for antidiabetic therapeutic interventions.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>\",\"PeriodicalId\":676,\"journal\":{\"name\":\"Journal of the Iranian Chemical Society\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-07-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the Iranian Chemical Society\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s13738-024-03067-x\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the Iranian Chemical Society","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s13738-024-03067-x","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Synthesis of novel oxadiazole derivatives: DFT calculations, molecular docking studies, and in vitro, in vivo evaluation of antidiabetic activity using Drosophila melanogaster model
Current antidiabetic medications have a plethora of harmful side effects, and most of the drugs do not contain 1,3,4-oxadiazole moiety. Therefore, research into the development of novel drugs which contain 1,3,4-oxadiazole moiety with fewer side effects is necessary. Novel fluorine-incorporated 1,3,4-oxadiazole derivatives (1c–1n) were synthesized, characterized, and evaluated for α-amylase and α-glucosidase enzyme inhibitor activity. An in vivo Drosophila melanogaster model and an in vitro system were used to investigate its antidiabetic properties, further, which were characterized by 1HNMR, MASS, and FT-IR. Spectroscopic techniques and DFT are used to calculate more geometrically optimized molecule structures using the B3LYP technique. The compounds were tested against the α-glucosidase and α-amylase enzymes. Among different compounds tested, compounds 1i (IC50 = 54.83 µg/ml), 1k (IC50 = 64.95 µg/ml), 1m (IC50 = 64.78 µg/ml), and 1n (IC50 = 66.30 µg/ml) showed significant α-amylase inhibitor efficacy compared to the acarbose (IC50 = 35.17 µg/ml); compounds 1m (IC50 = 74.64 µg/ml) and 1i (IC50 = 60.35 µg/ml) exhibited significant α-glucosidase inhibitory action compared to acarbose (IC50 = 46.06 µg/ml). The docking study exhibited that compound 1i creates six hydrogen bonds and compound 1m forms three hydrogen bonding contacts at the active site of the enzyme (PDBID:4w93). The obtained results are demonstrated that compounds 1i, 1m, 1n, and 1k had greater antidiabetic activities and can be further taken into consideration for antidiabetic therapeutic interventions.
期刊介绍:
JICS is an international journal covering general fields of chemistry. JICS welcomes high quality original papers in English dealing with experimental, theoretical and applied research related to all branches of chemistry. These include the fields of analytical, inorganic, organic and physical chemistry as well as the chemical biology area. Review articles discussing specific areas of chemistry of current chemical or biological importance are also published. JICS ensures visibility of your research results to a worldwide audience in science. You are kindly invited to submit your manuscript to the Editor-in-Chief or Regional Editor. All contributions in the form of original papers or short communications will be peer reviewed and published free of charge after acceptance.