Huang Lin, Huang Rong, Pang Fuhua, Li Anke, Huang Guobao, Zhou Xiaoqun, Li Qian, Li Fangyao, Ma Xianli
School of Pharmacy, Guilin Medical University Guilin Guangxi 541004 PR China
Guangxi Key Lab of Agricultural Resources Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University Yulin Guangxi 537000 PR China.
RSC Adv. 2020 May 11;10(31):18008-18015. doi: 10.1039/d0ra02432e. eCollection 2020 May 10.
A series of novel dehydroabietic acid derivatives containing pyrimidine moieties were designed and synthesized to explore more efficacious and less toxic antitumor agents according to the principle of combination and hybridization. The cytotoxicity against human liver cancer (HepG2) cells, human breast cancer (MCF-7) cells, human colon cancer (HCT-116) cells, human lung cancer (A549) cells, and human normal liver cells (LO2) was estimated by MTT assay . Cytotoxic activity screening revealed that most of the compounds showed moderate to high levels of cytotoxicity against these four cancer cell lines and that some displayed more potent inhibitory activities compared with 5-FU. In particular, compound 3b exhibited promising cytotoxicity with IC values ranging from 7.00 to 11.93 μM against all the tested cell lines and displayed weak cytotoxicity towards normal cells. Besides, cell cycle analysis indicated that compound 3b mainly arrested MCF-7 cells at the S stage and induced cell apoptosis.
根据组合与杂化原理，设计并合成了一系列含嘧啶基团的新型脱氢枞酸衍生物，以探索更有效且毒性更低的抗肿瘤药物。采用MTT法评估其对人肝癌（HepG2）细胞、人乳腺癌（MCF-7）细胞、人结肠癌（HCT-116）细胞、人肺癌（A549）细胞和人正常肝细胞（LO2）的细胞毒性。细胞毒性活性筛选显示，大多数化合物对这四种癌细胞系表现出中度至高度的细胞毒性，并且一些化合物与5-氟尿嘧啶相比表现出更强的抑制活性。特别是，化合物3b对所有测试细胞系均表现出有前景的细胞毒性，IC值范围为7.00至11.93μM，对正常细胞表现出较弱的细胞毒性。此外，细胞周期分析表明，化合物3b主要使MCF-7细胞停滞于S期并诱导细胞凋亡。
