AUTHOR=Hou Xi-Xi , Mao Long-Fei , Guo Yajie , Lou Chaoxuan , Wang Lan , Li Rui-Fang , Wang Huili , Li San-Qiang , Yang Jian-Xue TITLE=Design, synthesis and antitumour activity evaluation of novel dolutegravir derivatives JOURNAL=Frontiers in Pharmacology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1238587 DOI=10.3389/fphar.2023.1238587 ISSN=1663-9812 ABSTRACT=

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 4b and 4g were the most effective, and inhibited the growth of A549 cells with IC50 values of 8.72 ± 0.11 μM and 12.97 ± 0.32 μM, respectively. In addition, compound 4g induced apoptosis and clonal suppression in A549 tumor cells. Compound 4g 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.