Nano Alvand Company, Avicenna Tech Park, Tehran University of Medical Sciences, Tehran, Iran.
Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
Arch Pharm (Weinheim). 2020 Oct;353(10):e2000109. doi: 10.1002/ardp.202000109. Epub 2020 Jul 9.
Coumarins and their derivatives are receiving increasing attention due to numerous biochemical and pharmacological applications. In this study, a series of novel coumarin-1,2,3-triazole-acetamide hybrids was tested against some metabolic enzymes including α-glycosidase (α-Gly), α-amylase (α-Amy), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), human carbonic anhydrase I (hCA I), and hCA II. The new coumarin-1,2,3-triazole-acetamide hybrids showed K values in the range of 483.50-1,243.04 nM against hCA I, 508.55-1,284.36 nM against hCA II, 24.85-132.85 nM against AChE, 27.17-1,104.36 nM against BChE, 590.42-1,104.36 nM against α-Gly, and 55.38-128.63 nM against α-Amy. The novel coumarin-1,2,3-triazole-acetamide hybrids had effective inhibition profiles against all tested metabolic enzymes. Also, due to the enzyme inhibitory effects of the new hybrids, they are potential drug candidates to treat diseases such as epilepsy, glaucoma, type-2 diabetes mellitus (T2DM), Alzheimer's disease (AD), and leukemia. Additionally, these inhibition effects were compared with standard enzyme inhibitors like acetazolamide (for hCA I and II), tacrine (for AChE and BChE), and acarbose (for α-Gly and α-Amy). Also, those coumarin-1,2,3-triazole-acetamide hybrids with the best inhibition score were docked into the active site of the indicated metabolic enzymes.
香豆素及其衍生物因其具有许多生化和药理学应用而受到越来越多的关注。在这项研究中，一系列新型香豆素-1,2,3-三唑-乙酰胺杂合体能抑制一些代谢酶，包括α-葡萄糖苷酶（α-Gly）、α-淀粉酶（α-Amy）、乙酰胆碱酯酶（AChE）、丁酰胆碱酯酶（BChE）、人碳酸酐酶 I（hCA I）和 hCA II。新型香豆素-1,2,3-三唑-乙酰胺杂合体对 hCA I 的 K 值在 483.50-1,243.04 nM 范围内，对 hCA II 的 K 值在 508.55-1,284.36 nM 范围内，对 AChE 的 K 值在 24.85-132.85 nM 范围内，对 BChE 的 K 值在 27.17-1,104.36 nM 范围内，对 α-Gly 的 K 值在 590.42-1,104.36 nM 范围内，对 α-Amy 的 K 值在 55.38-128.63 nM 范围内。新型香豆素-1,2,3-三唑-乙酰胺杂合体对所有测试的代谢酶均具有有效的抑制作用。此外，由于新杂合体对这些酶的抑制作用，它们可能成为治疗癫痫、青光眼、2 型糖尿病（T2DM）、阿尔茨海默病（AD）和白血病等疾病的潜在药物候选物。此外，还将这些抑制作用与标准酶抑制剂（如乙酰唑胺（用于 hCA I 和 II）、他克林（用于 AChE 和 BChE）和阿卡波糖（用于 α-Gly 和 α-Amy））进行了比较。此外，还对具有最佳抑制评分的那些香豆素-1,2,3-三唑-乙酰胺杂合体进行了对接，以进入指定代谢酶的活性部位。
