Design, synthesis, and anticancer evaluation of alkynylated pyrrole derivatives

Abstract

A series of alkynylated pyrrole derivatives were meticulously designed, drawing inspiration from the structure of 3-alkynylpyrrole-2,4-dicarboxylates, which were synthesized via a cyclization process involving methylene isocyanides and propiolaldehydes under mild conditions. These derivatives were subsequently subjected to evaluation for their anticancer properties against a panel of cell lines, including U251, A549, 769-P, HepG2, and HCT-116. According to the detailed analysis of structure-activity relationship, compound 12l emerged as the most promising molecule, with IC₅₀ values of 2.29 ± 0.18 and 3.49 ± 0.30 μM toward U251 and A549 cells, respectively. Subsequent mechanistic investigations revealed that compound 12l exerts its effects by arresting the cell cycle in the G0/G1 phase and inducing apoptosis specifically in A549 cells. These innovative alkynylated pyrrole derivatives hold the potential to serve as a valuable template for the discovery of novel anticancer molecules.

Keywords: alkynylated pyrroles; anticancer activity; apoptosis; cell cycle arrest.