Design, Synthesis, and Biological Activity Evaluation of Novel AZT and Adenosine-Derived 1,2,3-Triazoles

• Published in: Journal of chemistry Vol. 2023; pp. 1 - 17
• Main Authors: Le, Duc Anh, Truong, Ngoc Hung, Vu, Van Dung, Doan, Thanh Huyen, Le, Minh Tri, Nguyen, Thi Huong, Nguyen, Manh Cuong, Do, Huu Nghi, Ninh, Duc Bao, Le, Phong, Nguyen, Thi Phuong Thao, Tran, Khac Vu, Luu, Van Chinh
• Format: Journal Article
• Language: English
• Published: New York Hindawi 28.09.2023; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Acids; Adenosine; Alkynes; Biological activity; Cancer; Carbon; Chemistry; Copper; Cycloaddition; Cytotoxicity; Ethylenediaminetetraacetic acid; Hydrazines; Proteases; Severe acute respiratory syndrome coronavirus 2; Triazoles; Zidovudine; Vietnam; Germany
• ISSN: 2090-9063; 2090-9071
• DOI: 10.1155/2023/1605316

CuSO4/hydrazine hydrate was used as a catalyst system for copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) of AZT and 5′-azido adenosine with terminal alkynes to give 30 novel 1,2,3-triazole derivatives. Screening for their anticancer, anti-inflammatory, angiotensin-converting enzyme 2 (ACE2), and 3C-like protease (3CLpro) inhibitory activities showed that several triazoles of AZT containing murayafoline A and indirubin-3′-oxime inhibited the growth of HepG2 and LU-1 with the IC50 values ranging from 11.01 to 19.87 μg/mL. Besides that, some triazole derivatives of adenosine exhibited anti-inflammatory activity against RAW264.7 cells with the IC50 values within an interval of 12.00–59.48.00 μg/mL. Especially, two triazoles of adenosine with indirubin-3′-oxime at O- and N1 positions expressed the ACE2 and 3CLpro inhibitory activities in which the triazole of adenosine with indirubin-3′-oxime at N1 inhibited both ACE2 and 3CLpro inhibitory activities with IC50 values of 135.62 and 142.95 μg/mL, respectively.