Potent EGFR/PARP-1 inhibition by spirooxindole-triazole hybrids for targeted liver cancer therapy.

ABSTRACT: The search for effective anti-cancer therapies has led to the exploration of dual inhibition strategies targeting multiple key molecular pathways. In this study, we aimed to design a novel candidate capable of dual inhibition targeting both EGFR (Epidermal Growth Factor Receptor) and PARP-1 (poly(ADP-ribose)polymerase-1), two crucial proteins implicated in cancer progression and resistance mechanisms. Through molecular hybridization and structure-based drug design approaches, we synthesized a series of compounds based on spirooxindole with triazole scaffolds with the potential for dual EGFR and PARP-1 inhibition. Interestingly, compounds 4a, 4b and 4f showed potent cytotoxicity against HepG2 cells with IC₅₀ values of 3.6, 4.6, and 1.9 μM compared to doxorubicin (IC₅₀

SUBMITTER: Nafie MS 

PROVIDER: S-EPMC11701428 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature