Design, synthesis, and anticancer evaluation of alkynylated pyrrole derivatives

• Published in: Chemical biology & drug design 2024-02, Vol.103 (2), p.e14484-n/a
• Main Authors: Wei, Hegeng, Cao, Yu, Zhao, Chungang, Shao, Zhanying, Huo, Xiaoli, Pan, Jinming, Zhuang, Rangxiao
• Format: Article
• Language: English
• Subjects: alkynylated pyrroles; anticancer activity; Antineoplastic Agents - chemistry; Apoptosis; cell cycle arrest; Cell Line, Tumor; Cell Proliferation; Drug Design; Drug Screening Assays, Antitumor; Molecular Structure; Pyrroles - chemistry; Structure-Activity Relationship
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.14484

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. The discovery of alkynylated pyrrole derivatives as anticancer agents.