Design and synthesis of cabotegravir derivatives bearing 1,2,3-triazole and evaluation of anti-liver cancer activity

Abstract

Based on the structure of the anti-HIV drug cabotegravir, we introduced 1,2,3-triazole groups with different substituents to obtain 19 cabotegravir derivatives and tested their activity against HepG2 cells. The proliferation of HepG2 cells was examined following treatment with derivatives. Most of the compounds demonstrated significant inhibitory effects, particularly compounds KJ-5 and KJ-12 with IC50 values of 4.29 ± 0.10 and 4.07 ± 0.09 μM, respectively. Furthermore, both compounds 5 and 12 significantly caused cell apoptosis, G2/M arrest, and DNA damage, and suppressed invasion and migration in a concentration-dependent manner. In addition, KJ-5 and KJ-12 could trigger apoptosis via the mitochondrial pathway by increasing the ratio of Bax/Bcl-2 and activating cleaved caspase-9, cleaved caspase-3, and cleaved PARP.

Lamivudine, Doravirine, and Cabotegravir Downregulate the Expression of Human Endogenous Retroviruses (HERVs), Inhibit Cell Growth, and Reduce Invasive Capability in Melanoma Cell Lines

“…Its high efficacy at low doses and the high satisfaction reported by individuals living with HIV make it a very promising drug for long-term treatment [60]. Interestingly, some triazole analogues of cabotegravir were recently synthesized and tested in vitro for their antitumor activity against non-small-cell lung cancer cells [61] and a hepatocellular carcinoma cell line [62]. These results, along with our findings, suggest that the potential of cabotegravir in melanoma therapy deserves organoids and/or in vivo investigations.…”

Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives

“…Furthermore, both KJ-5 and KJ-12 were found to induce apoptosis via the mitochondrial pathway and inhibit the invasion and migration of cancer cells. [ 19 ]. By utilizing the structural features of the EGFR inhibitor erlotinib, compounds a1–a22 with erlotinib-1,2,3-triazole derivatives were obtained through click reactions [ 20 ].…”