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

IF 2.2 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY Journal of the Iranian Chemical Society Pub Date : 2024-07-26 DOI:10.1007/s13738-024-03067-x
Govinda Anjanayya, Ramesh Gani, Avinash Kudva, Shrinivas Joshi, Murigendra Hiremath, Apsara Kavital, Karabasanagouda Timanagouda, Basavarajaiah Mathada, Mohammad Javeed, Raifa Aziz, Shamprasad Raghu
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引用次数: 0

摘要

目前的抗糖尿病药物有许多有害的副作用,而且大多数药物都不含 1,3,4-恶二唑分子。因此,有必要研究开发含有 1,3,4-恶二唑分子且副作用较小的新型药物。研究人员合成了新型含氟 1,3,4-噁二唑衍生物(1c-1n),对其进行了表征,并评估了其对α-淀粉酶和α-葡萄糖苷酶的抑制活性。此外,还利用体内黑腹果蝇模型和体外系统研究了它的抗糖尿病特性,并通过 1HNMR、MASS 和 FT-IR 对其进行了表征。利用光谱技术和 DFT,采用 B3LYP 技术计算出了更优化的分子几何结构。对这些化合物进行了抗α-葡萄糖苷酶和α-淀粉酶测试。在测试的不同化合物中,化合物 1i(IC50 = 54.83 µg/ml)、1k(IC50 = 64.95 µg/ml)、1m(IC50 = 64.78 µg/ml)和 1n(IC50 = 66.30 µg/ml)与阿卡波糖(IC50 = 35.17 µg/ml)相比,化合物 1m(IC50 = 74.64 µg/ml)和 1i(IC50 = 60.35 µg/ml)表现出明显的α-葡萄糖苷酶抑制作用。对接研究表明,化合物 1i 在酶的活性位点上形成了六个氢键,化合物 1m 在活性位点上形成了三个氢键接触(PDBID:4w93)。研究结果表明,化合物 1i、1m、1n 和 1k 具有较强的抗糖尿病活性,可进一步考虑用于抗糖尿病治疗干预。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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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.

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CiteScore
4.40
自引率
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230
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5.6 months
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.
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