Design, synthesis and antitumour activity evaluation of novel dolutegravir derivatives

Based on the modification of the structure of dolutegravir, we introduced 1,2,3triazole 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 mu M and 12.97 +/- 0.32 mu M, 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 gamma-H2AX signaling pathway to induce DNA damage in tumor cells.

Automated summary

Based on structural modification, novel dolutegravir derivatives containing 1,2,3-triazole moieties with different substituted groups were synthesized. The derivatives exhibited good inhibitory effects on A549 cells, with compounds 4b and 4g being the most effective, showing IC50 values of 8.72 +/- 0.11 mu M and 12.97 +/- 0.32 mu M, respectively. Furthermore, compound 4g induced apoptosis and clonal suppression in A549 tumor cells, activated LC3 signaling pathway to induce autophagy, and activated gamma-H2AX signaling pathway to induce DNA damage in tumor cells.