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探索噻唑烷二酮-萘类似物作为潜在抗糖尿病药物:设计、合成、分子对接及体外评价

Exploring Thiazolidinedione-Naphthalene Analogues as Potential Antidiabetic Agents: Design, Synthesis, Molecular Docking and In-vitro Evaluation.

作者信息

Mohd Sharfuddin, Sharma Vikas, Harish Vancha, Kumar Rakesh, Pilli Govindaiah

机构信息

School of pharmaceutical sciences, Lovely Professional University, Phagwara, Punjab, India.

Faculty of medicine, Department of Pathology, Wayne state University, Detroit, MI, USA.

出版信息

Cell Biochem Biophys. 2025 Jun;83(2):2213-2226. doi: 10.1007/s12013-024-01632-y. Epub 2024 Dec 13.

Abstract

Thiazolidinedione-naphthalene analogues were synthesized and evaluated for antidiabetic activity as Pancreatic α-Amylase (PAA) and intestinal α-glucosidase (IAG) inhibitors. The activity of the compounds (14a-g,17a-k) is compared with acarbose as the standard drug and all the compounds shows good to moderate antidiabetic activity. In-vitro PAA and IAG inhibition assay is performed for the all compounds, the compounds 17e shows superior PAA and IAG inhibitory activity with respective to standard (IC = 12.455 ± 0.04 μM and 9.145 ± 0. 01 μM). The molecular interaction with PAA and IAG protein was also studied with the help of molecular docking studies using AutoDock software. while SwissADME and Osiris property explorer tools computed in-silico drug likeliness and toxicity properties. The in-silico results confirmed the 17e molecule as a superior drug with high binding affinity and good drug likeness against PAA and IAG, confirming in-vitro results. We also studied antioxidant activity (AOA) of all synthesized compounds and results confined that the compound 14g and 17e has good antioxidant potential IC = 8.04 ± 0.02 μM and 6.36 ± 0.03 μM respectively among all compounds. In conclusion, in-vitro, in-silico antidiabetic and antioxidant studies revealed 17e compound was found to be potential compound.

摘要

合成了噻唑烷二酮-萘类似物,并作为胰腺α-淀粉酶(PAA)和肠道α-葡萄糖苷酶(IAG)抑制剂评估其抗糖尿病活性。将化合物(14a-g,17a-k)的活性与作为标准药物的阿卡波糖进行比较,所有化合物均表现出良好至中等的抗糖尿病活性。对所有化合物进行了体外PAA和IAG抑制试验,化合物17e相对于标准品显示出优异的PAA和IAG抑制活性(IC = 12.455±0.04μM和9.145±0.01μM)。还借助使用AutoDock软件的分子对接研究,研究了与PAA和IAG蛋白的分子相互作用。同时,利用SwissADME和Osiris性质探索工具计算了计算机辅助药物相似性和毒性性质。计算机辅助结果证实17e分子是一种对PAA和IAG具有高结合亲和力和良好药物相似性的优质药物,证实了体外实验结果。我们还研究了所有合成化合物的抗氧化活性(AOA),结果表明化合物14g和17e在所有化合物中分别具有良好的抗氧化潜力,IC值分别为8.04±0.02μM和6.36±0.03μM。总之,体外、计算机辅助抗糖尿病和抗氧化研究表明,17e化合物是一种有潜力的化合物。

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