Synthesis, characterization, molecular docking, and biological activities of coumarin–1,2,3‐triazole‐acetamide hybrid derivatives
Nima Sepehri, Maryam Mohammadi‐Khanaposhtani, Nafise Asemanipoor, Samanesadat Hosseini, Mahmood Biglar, Bagher Larijani, Mohammad Mahdavi, Haleh Hamedifar, Parham Taslımı, Nastaran Sadeghian, İlhami Gülçın
Abstract
Abstract 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 i 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.