Chu Pei-Yi, Pan Yi-Cheng, Hsu Wei-Yu, Chuang Da-Wei, Yang Juan-Cheng, Chen Guan-Yu, Jang Yeong-Jiunn, Wu Yang-Chang
Chinese Medicine Research and Development Center, China Medical University Hospital Taichung 404332 Taiwan
Division of Pharmaceutical Science, Center for Drug Evaluation Taipei 11557 Taiwan.
RSC Med Chem. 2025 Aug 28. doi: 10.1039/d5md00349k.
Natural products are an important source for developing anti-cancer agents. Previously, we identified the anti-cancer flavonoid protoapigenone from (Gaud.) and synthesized its derivative, WYC-0209, with improved anti-cancer properties. In this study, to further optimize this protoapigenone derivative for better therapeutic efficacy, various functional groups were introduced onto its naphthalene ring, and their anti-cancer properties were evaluated. A total of eighteen WYC-0209 derivatives were synthesized, among which the derivative containing two units of the isopentyl-substituted side chain exhibited superior cytotoxicity against cancer cells and was named WYC-241. Further investigation in A549 lung cancer cells showed that WYC-241 significantly inhibited colony formation (proliferation) and suppressed cell migration (mobility). Additionally, WYC-241 induced both necrosis and apoptosis, potentially through a substantial increase in intracellular reactive oxygen species (ROS) levels and inhibition of the PI3K/AKT pathway. studies showed that weekly intravenous (i.v.) injection of WYC-241 significantly suppressed tumor growth in mice. ADMET analysis further indicated that WYC-241 possesses drug-like properties. Collectively, this study suggests that WYC-241 is a promising candidate for further development as a novel anti-cancer therapy and provides a foundation for future drug design and optimization.
天然产物是开发抗癌药物的重要来源。此前，我们从[植物名称]中鉴定出抗癌黄酮原芹菜素，并合成了其衍生物WYC - 0209，其抗癌特性有所改善。在本研究中，为了进一步优化该原芹菜素衍生物以获得更好的治疗效果，在其萘环上引入了各种官能团，并评估了它们的抗癌特性。总共合成了18种WYC - 0209衍生物，其中含有两个异戊基取代侧链单元的衍生物对癌细胞表现出优异的细胞毒性，被命名为WYC - 241。在A549肺癌细胞中的进一步研究表明，WYC - 241显著抑制集落形成（增殖）并抑制细胞迁移（运动性）。此外，WYC - 241诱导坏死和凋亡，可能是通过细胞内活性氧（ROS）水平的大幅增加和PI3K/AKT途径的抑制。体内研究表明，每周静脉注射WYC - 241可显著抑制小鼠肿瘤生长。ADMET分析进一步表明WYC - 241具有类药物特性。总体而言，本研究表明WYC - 241作为一种新型抗癌疗法有进一步开发的潜力，并为未来的药物设计和优化提供了基础。
