Noscapine-bile acid hybrids as novel anticancer agents

Abstract

Twenty novel noscapinoid–triterpene conjugate derivatives were designed and synthesized. Four noscapine derivatives (as secondary amine) and five bile acids were applied for the synthesis of a diverse library. The synthetic compounds were evaluated for their antiproliferative activity against PC3, A549, HepG2, Caki-1, U138MG, and MRC5. This study identified eight potent cytotoxic agents (7e–7i, 7k, 7m, and 7o) possessing more than 80% cell viability. Compounds 7e and 7f exhibited the highest cytotoxic activity against Caki-1 with IC₅₀ values of 260 nM and 350 nM, respectively. Western blot analysis results indicated that the eight hit compounds decreased the α-tubulin and β-actin levels in A549 cells, and further cellular assays on A549 demonstrated that 7e and 7f significantly inhibited cell migration, induced pronounced G1 cell-cycle arrest (with 7f also showing a minor G2/M increase) and triggered marked apoptosis, with 7e showing the strongest pro-apoptotic effect.