取代乙酸己_庚_硫酯类化合物的合成与体外抗肿瘤活性_闻家辰.pdfVIP

352 Acta Pharmaceutica Sinica 2014, 49 (3): 352−358 () 1 1 2 1 1 1 1* , , , , , , ( 1. , 2. , 110016) : apicidin , , () 26 1H NMRIRMS HR-MS MTT , , II-1II-3II-6II-13 HL-60 , IC50 , II-7II-8 MCF-7 , IC50 3.19 6.29 µmol·L−1 : apicidin; ; ; : R916 : A : 0513-4870 (2014) 03-0352-07 Synthesis and antitumor activity of S-hexyl(heptyl) substituted ethanethioate derivatives 1 1 2 1 1 1 1* WEN Jia-chen , JIANG Tao , BAO Yu , LIN Xian-jun , WANG Wan-qiao , LIU Dan , ZHAO Lin-xiang (1. Key Laboratory of Structure-Based Drugs Design Discovery of Ministry of Education, 2. School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China) Abstract : To simplify the macrocyclic fragment and to modify the zinc binding group of the natural product apicidin, two series of S-hexyl (heptyl) ethanethioate derivatives were designed and synthesized. Twenty-six compounds were synthesized and confirmed with 1H NMR, IR, MS and HR-MS spectrum, which were not reported. Take vorinostat as control, their antiporliferative activities against cancer cell lines, MCF-7 and HL-60, were tested with MTT assay or trypan blue staining method. Generally in both series it was found that, the chiral carbon atom at 7 position is not necessary, compounds II-1, II-3, II-6 and II-13 showed good activity on HL-60 cells in vitro, with the IC50 values less