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- Title
Studying the Structure and Evaluating α‐Glucosidase Inhibition of Novel Acetamide Derivatives Incorporating 4‐Ethyl‐4H‐1,2,4‐Triazole Starting from 2‐(Naphthalen‐1‐yl)Acetic Acid.
- Authors
Le, Trong Duc; Nguyen, Tien Cong; Tran, Thi Minh Dinh; Hoang, Thi Kim Dung; To, Khanh Duong; Nguyen, Minh Phuong Hien; Tran, Thi My Ngan; Dinh, Chau Phi; Alhaji, Jibril Abdullahi; Van Meervelt, Luc
- Abstract
This research aims to create innovative compounds that incorporate 1,2,4‐triazole and exhibit α‐glucosidase inhibitory potential. Similar to our previously reported series of N‐aryl 2‐{[5‐(naphthalen‐1‐ylmethyl)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl]thio}acetamide compounds, we explore here 4‐ethyl instead of 4‐phenyl as substituent. The synthesis process effectively yielded these compounds, with the highest yield reaching up to 91 % for compound N‐phenyl‐2‐{[5‐(naphthalen‐1‐ylmethyl)‐4‐ethyl‐4H‐1,2,4‐triazol‐3‐yl]thio}acetamide 5 a. Their structures were validated through various spectroscopic techniques such as IR, 1H‐NMR, 13C‐NMR, and HR‐MS spectra, and for compounds 3, 5 d, and 5 e by X‐ray diffraction. In vitro experiments revealed that only compound 5 g, marked by a 3‐hydroxy substitution on the N‐phenylacetamide moiety, demonstrated higher α‐glucosidase inhibitory potential (IC50=158.4±3.4 μM) compared to the positive control, acarbose (IC50=351.3±1.8 μM). Molecular docking studies also coincide with in vitro assay by uncovering a strong hydrogen bond with residue Asp1526 along with other hydrophobic interactions of compound 5 g in the α‐glucosidase binding pocket. Compound 5 g showed a free binding energy of −9.7 kcal/mol, contrasting with acarbose (−8.0 kcal/mol). Despite the modest biological activity, this research underscores the simplicity and convenience of the procedure for synthesizing 1,2,4‐triazole‐based compounds, and contributes a key feature to the structure‐activity relationship of the triazole scaffold in the α‐glucosidase pocket.
- Subjects
ACETAMIDE derivatives; ACETIC acid; ACETAMIDE; HYDROPHOBIC compounds; HYDROPHOBIC interactions; STRUCTURE-activity relationships
- Publication
Asian Journal of Organic Chemistry, 2024, Vol 13, Issue 6, p1
- ISSN
2193-5807
- Publication type
Article
- DOI
10.1002/ajoc.202400063