Molecular Diversity ( IF 3.9 ) Pub Date : 2021-10-04 , DOI: 10.1007/s11030-021-10314-3 Hina Siddiqui 1 , M A A Baheej 2 , Saeed Ullah 3 , Fazila Rizvi 1 , Shazia Iqbal 1 , Haroon M Haniffa 2 , Atia-Tul Wahab 3 , M Iqbal Choudhary 1, 3, 4, 5
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The current study was aimed to discover potent inhibitors of α-glucosidase enzyme. A 25 membered library of new 1,2,3-triazole derivatives of hydrochlorothiazide (1) (HCTZ, a diuretic drug also being used for the treatment of high blood pressure) was synthesized through click chemistry approach. The structures of all derivatives 2–26 were deduced by MS, IR, 1H-NMR, and 13C-NMR spectroscopic techniques. All the compounds were found to be new. Compounds 1–26 were evaluated for α-glucosidase enzyme inhibition activity. Among them, 18 compounds showed potent inhibitory activity against α-glucosidase with IC50 values between 24 and 379 µM. α-Glucosidase inhibitor drug acarbose (IC50 = 875.75 ± 2.08 μM) was used as the standard. Kinetics studies of compounds 6, 9, 11, 12, 15, 20, 23, and 24 revealed that only compound 15 as a mixed-type of inhibitor, while others were non-competitive inhibitors of α-glucosidase enzyme. All the compounds were found to be non-cytotoxic when checked against mouse fibroblast 3T3 cell line.
Graphic abstract
中文翻译：
通过点击化学方法和体外 α-葡萄糖苷酶抑制研究合成 1,2,3,三唑修饰的氢氯噻嗪类似物
目前的研究旨在发现有效的α-葡萄糖苷酶抑制剂。通过点击化学方法合成了氢氯噻嗪的新 1,2,3-三唑衍生物 ( 1 )（HCTZ，一种也用于治疗高血压的利尿药物）的25成员库。通过 MS、IR、1 H-NMR 和13 C-NMR 光谱技术推断所有衍生物2-26的结构。发现所有化合物都是新的。评估了化合物1-26的 α-葡萄糖苷酶抑制活性。其中，18 种化合物对 α-葡萄糖苷酶具有有效的抑制活性，IC 50值在 24 和 379 µM 之间。α-葡萄糖苷酶抑制剂药物阿卡波糖 (IC 50 = 875.75 ± 2.08 μM) 用作标准。化合物 6、9、11、12、15、20、23 和 24的动力学研究表明，只有化合物15作为混合型抑制剂，而其他化合物是α-葡萄糖苷酶的非竞争性抑制剂。当针对小鼠成纤维细胞 3T3 细胞系进行检查时，发现所有化合物均无细胞毒性。
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