Novel pyrrolizines bearing 3,4,5-trimethoxyphenyl moiety: design, synthesis, molecular docking, and biological evaluation as potential multi-target cytotoxic agents.

ABSTRACT: In the present study, two new series of pyrrolizines bearing 3,4,5-trimethoxyphenyl moiety were designed, synthesised, and evaluated for their cytotoxic activity. The benzamide derivatives 16a-e showed higher cytotoxicity than their corresponding Schiff bases 15a-e. Compounds 16a,b,d also inhibited the growth of MCF-7/ADR cells with IC₅₀ in the range of 0.52-6.26 μM. Interestingly, the new compounds were less cytotoxic against normal MRC-5 cells (IC₅₀=0.155-17.08 μM). Mechanistic studies revealed the ability of compounds 16a,b,d to inhibit tubulin polymerisation and multiple oncogenic kinases. Moreover, compounds 16a,b,d induced preG₁ and G₂/M cell cycle arrest and early

SUBMITTER: Shawky AM 

PROVIDER: S-EPMC8221158 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature