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=<p>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 <bold>4b</bold> and <bold>4g</bold> were the most effective, and inhibited the growth of A549 cells with IC<sub>50</sub> values of 8.72 ± 0.11 μM and 12.97 ± 0.32 μM, respectively. In addition, compound <bold>4g</bold> induced apoptosis and clonal suppression in A549 tumor cells. Compound <bold>4g</bold> 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.</p>