Design, synthesis and antitumor activity of triphenylphosphonium-linked derivatives of quinazolinone

• Published in: Natural product research 2024-11, p.1-6
• Main Authors: Wang, Qianqian, Chen, Ruofan, Wang, Rui, Huang, Jianjun, Xu, Yinuo, Wang, Na, Li, Deshang, Xu, Chenmeng, Wang, Bo, Li, Yi, Dehaen, Wim, Huai, Qiyong
• Format: Article
• Language: English
• ISSN: 1478-6419; 1478-6427; 1478-6427
• DOI: 10.1080/14786419.2024.2426206

Cancer is the leading cause of human death. Quinazolinone heterocyclic compounds have a variety of biological activities and have been extensively studied in recent years, especially for their potential anticancer activity. The triphenylphosphonium moiety (TPP ) has become a very important lipophilic cation, especially concerning its application the development of anticancer agents. In this work, we designed and synthesised 24 new TPP -conjugated quinazolinone derivatives, which have alkylated TPP at the N-3 position and different small group substitutions at the C-6 position, and their antiproliferative activity was evaluated in three cancer cell lines (human alveolar adenocarcinoma cells (A549), human hepatoblastoma cells (HepG2) and human breast cancer cells (MCF-7)) and human normal liver cells (QSG-7701). The cytotoxicity screening results showed that some derivatives exhibited effective inhibitory effects in cancer cells. Among them, the compound - showed better antiproliferative activity than the positive control drug gefitinib on MCF-7 and A549 cells. The most active compounds being , with IC values of 6.56, 14.52 and 7.51 µM in MCF-7 cells, HepG2 cells and A549 cells, respectively. Compound may be a promising compound for cancer treatment worthy of further study.