Design, synthesis and antitumour activity evaluation of novel dolutegravir derivatives

• Published in: Frontiers in pharmacology Vol. 14; p. 1238587
• Main Authors: Hou, Xi-Xi, Mao, Long-Fei, Guo, Yajie, Lou, Chaoxuan, Wang, Lan, Li, Rui-Fang, Wang, Huili, Li, San-Qiang, Yang, Jian-Xue
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 07.08.2023
• Subjects: 1,2,3-triazole; antitumor; autophagy; DNA damage; dolutegravir; Pharmacology; autophagy; dolutegravir; antitumor; 1,2,3-triazole; DNA damage
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2023.1238587

Based on the modification of the structure of dolutegravir, we introduced 1,2,3-triazole moieties with different substituted groups and obtained a lot of novel dolutegravir derivatives. The activity of A549 cells treated with the derivatives was examined, and most compounds showed good inhibitory effects. Among them, compounds and were the most effective, and inhibited the growth of A549 cells with IC values of 8.72 ± 0.11 μM and 12.97 ± 0.32 μM, respectively. In addition, compound induced apoptosis and clonal suppression in A549 tumor cells. Compound also activated the LC3 signaling pathway to induce autophagy in tumor cells, and activated the γ-H2AX signaling pathway to induce DNA damage in tumor cells.