药学学报, 2012, 47(8): 1017-1022
引用本文:
胡国强, 侯莉莉, 王国强, 段楠楠, 温晓漪, 曹铁耀, 银 俊, 王 伟, 谢松强, 黄文龙. 氟喹诺酮C-3杂环化合物的设计、合成与抗肿瘤活性研究: 环丙沙星双-噁二唑甲硫醚衍生物[J]. 药学学报, 2012, 47(8): 1017-1022.
. Part IV: design, synthesis and antitumor activity of fluoroquinolone C-3 heterocycles: bis-oxadiazole methylsulfide derivatives derived from ciprofloxacin[J]. Acta Pharmaceutica Sinica, 2012, 47(8): 1017-1022.

氟喹诺酮C-3杂环化合物的设计、合成与抗肿瘤活性研究: 环丙沙星双-噁二唑甲硫醚衍生物
胡国强1*, 侯莉莉1, 王国强1, 段楠楠1, 温晓漪1, 曹铁耀1, 银 俊1, 王 伟1, 谢松强1, 黄文龙2
(1. 河南大学化学生物学研究所, 河南 开封 475001; 2. 中国药科大学新药研究中心, 江苏 南京 210009)
摘要:

为进一步探究发现抗肿瘤氟喹诺酮候选化合物的有效策略, 用噁二唑杂环作为环丙沙星的羧基电子等排体得中间体C-3噁二唑硫醇 (5), 与噁二唑氯甲烷 (6a6h) 缩合形成双-噁二唑甲硫醚 (7a7h), 再与碘甲烷成哌嗪季铵盐 (8a8h), 其结构经元素分析和光谱数据确证, 评价了体外对CHOHL60L1210 3种肿瘤细胞的生长抑制活性。初步的药理结果表明, 哌嗪季铵盐 (8) 的活性高于相应游离碱 (7) 的活性。

关键词:   
Part IV: design, synthesis and antitumor activity of fluoroquinolone C-3 heterocycles: bis-oxadiazole methylsulfide derivatives derived from ciprofloxacin
Abstract:

To explore an efficient strategy for further development of anticancer fluoroquinolone candidates derived from ciprofloxacin, a heterocyclic ring as the bioisosteric replacement of C3 carboxyl group led to a key intermediate, oxadiazole thiol (5), which was further modified to the bis-oxadiazole methylsulfides (7a7h) and the corresponding dimethylpiperazinium iodides (8a8h), respectively. Structures were characterized by elemental analysis and spectra data, and their anticancer activities in vitro against CHO, HL60 and L1210 cancer cells were also evaluated by MTT assay.  The preliminary results show that piperazinium compounds (8) possess more potent activity than that of corresponding free bases (7).

Key words:   
收稿日期:
相关功能
PDF(318KB) Free
打印本文
0
作者相关文章