Hsieh Min-Tsang, Chang Ling-Chu, Hung Hsin-Yi, Lin Hui-Yi, Shih Mei-Hui, Tsai Chang-Hai, Kuo Sheng-Chu, Lee Kuo-Hsiung
Chinese Medicinal Research and Development Center, China Medical University and Hospital, Taichung 404, Taiwan; School of Pharmacy, China Medical University, Taichung 404, Taiwan.
Chinese Medicinal Research and Development Center, China Medical University and Hospital, Taichung 404, Taiwan.
Eur J Med Chem. 2017 May 5;131:141-151. doi: 10.1016/j.ejmech.2017.03.006. Epub 2017 Mar 8.
Novel bis(hydroxymethyl) alkanoate curcuminoid derivatives were designed, synthesized and screened for in vitro antiproliferative and in vivo antitumor activity. Selected new compound 9a and curcumin were further evaluated for inhibitory activity against ER/PR breast cancer (MCF-7, T47D), HER 2 breast cancer (SKBR3, BT474, and MDA-MB-457) and triple negative breast cancer (TNBC) (HS-578T, MDA-MB-157, and MDA-MB-468) cell lines. In addition, compound 9a was evaluated in the MDA-MB-231 xenograft nude mice model. Compound 9a exhibited greater inhibitory activity than curcumin against TNBC cells and also demonstrated significant inhibitory activity against doxorubicin-resistant MDA-MB-231 cells, with ten-fold higher potency than curcumin. Furthermore, when evaluated against the MDA-MB-231 xenograft nude mice model, compound 9a alone was ten-fold more potent than curcumin. Moreover, synergistic activity was observed when 9a was used in combination with doxorubicin against MDA-MB-231 breast cancer cells.
设计、合成了新型双（羟甲基）链烷酸姜黄素衍生物，并对其进行体外抗增殖和体内抗肿瘤活性筛选。对选定的新化合物9a和姜黄素进一步评估其对雌激素受体/孕激素受体（ER/PR）乳腺癌（MCF-7、T47D）、人表皮生长因子受体2（HER 2）乳腺癌（SKBR3、BT474和MDA-MB-457）以及三阴性乳腺癌（TNBC）（HS-578T、MDA-MB-157和MDA-MB-468）细胞系的抑制活性。此外，在MDA-MB-231异种移植裸鼠模型中对化合物9a进行了评估。化合物9a对TNBC细胞表现出比姜黄素更强的抑制活性，并且对多柔比星耐药的MDA-MB-231细胞也表现出显著的抑制活性，效力比姜黄素高十倍。此外，在MDA-MB-231异种移植裸鼠模型中进行评估时，单独使用化合物9a的效力比姜黄素高十倍。此外，当9a与多柔比星联合用于MDA-MB-231乳腺癌细胞时，观察到协同活性。
