Li Defeng, Liu Chuanxu, Guo Tingyu, Zhu Jiajie, Guo Jiaqi, Luo Ting, Liu Yuhuan, Shen Wenhao, Jiang Biao, Wang Wei, Yin Qianqian, Zhang Yongqiang
Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, and School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P. R. China.
Department of Lymphoma, Fudan University Shanghai Cancer Center, Shanghai 200032, P. R. China.
ACS Med Chem Lett. 2024 Jan 5;15(2):230-238. doi: 10.1021/acsmedchemlett.3c00462. eCollection 2024 Feb 8.
Herein, we disclose a powerful strategy for the functionalization of the antitumor natural alkaloid noscapine by utilizing photoredox/nickel dual-catalytic coupling technology. A small collection of 37 new noscapinoids with diverse (hetero)alkyl and (hetero)cycloalkyl groups and enhanced sp character was thus synthesized. Further antiproliferative activity screening and SAR study enabled the identification of as a novel, potent, and less-toxic anticancer agent. Furthermore, exerts superior cellular activity via an unexpected S-phase arrest mechanism and could significantly induce cell apoptosis in a dose-dependent manner, thereby further highlighting its potential in drug discovery as a promising lead compound.
在此，我们披露了一种利用光氧化还原/镍双催化偶联技术对抗肿瘤天然生物碱那可丁进行官能团化的有效策略。由此合成了一小批37种具有不同（杂）烷基和（杂）环烷基基团且增强了sp特性的新那可丁类化合物。进一步的抗增殖活性筛选和构效关系研究使得能够鉴定出一种新型、高效且低毒的抗癌剂。此外，该化合物通过一种意想不到的S期阻滞机制发挥出卓越的细胞活性，并能以剂量依赖的方式显著诱导细胞凋亡，从而进一步突出了其作为一种有前景的先导化合物在药物研发中的潜力。
