含杂环部分的萝卜硫素类似物：合成及其对癌细胞系的抑制活性
Sulforaphane Analogues with Heterocyclic Moieties: Syntheses and Inhibitory Activities against Cancer Cell Lines.
作者信息
Shi Ye-Hui, Dai Dong-Fang, Li Jing, Dong Yan-Wei, Jiang Yin, Li Huan-Gong, Gao Yuan, Chong Chuan-Ke, Li Hui-Ying, Chu Xiao-Qian, Yang Cheng, Zhang Quan, Tong Zhong-Sheng, Bai Cui-Gai, Chen Yue
机构信息
Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, and Key Laboratory of Cancer Prevention and Therapy, Tianjin 30060, China.
The State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China.
出版信息
Molecules. 2016 Apr 21;21(4):514. doi: 10.3390/molecules21040514.
Recent studies have shown that sulforaphane (SFN) selectively inhibits the growth of ALDH⁺ breast cancer stem-like cells.Herein, a series of SFN analogues were synthesized and evaluated against breast cancer cell lines MCF-7 and SUM-159, and the leukemia stem cell-like cell line KG-1a. These SFN analogues were characterized by the replacement of the methyl group with heterocyclic moieties, and the replacement of the sulfoxide group with sulfide or sulfone. A growth inhibitory assay indicated that the tetrazole analogs 3d, 8d and 9d were significantly more potent than SFN against the three cancer cell lines. Compound 14c, the water soluble derivative of tetrazole sulfide 3d, demonstrated higher potency against KG-1a cell line than 3d. SFN, 3d and 14c significantly induced the activation of caspase-3, and reduced the ALDH⁺ subpopulation in the SUM159 cell line, while the marketed drug doxrubicin(DOX) increased the ALDH⁺ subpopulation.
近期研究表明，萝卜硫素（SFN）可选择性抑制乙醛脱氢酶阳性（ALDH⁺）乳腺癌干细胞样细胞的生长。在此，合成了一系列SFN类似物，并针对乳腺癌细胞系MCF-7和SUM-159以及白血病干细胞样细胞系KG-1a进行了评估。这些SFN类似物的特征在于用杂环部分取代甲基，并用硫化物或砜取代亚砜基团。生长抑制试验表明，四唑类似物3d、8d和9d对这三种癌细胞系的活性明显高于SFN。四唑硫化物3d的水溶性衍生物化合物14c对KG-1a细胞系的活性高于3d。SFN、3d和14c显著诱导半胱天冬酶-3的激活，并减少SUM159细胞系中ALDH⁺亚群，而市售药物阿霉素（DOX）则增加了ALDH⁺亚群。
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