氟喹诺酮(绕丹宁不饱和酮)酰胺衍生物的合成与抗肿瘤活性  

Synthesis and anti-proliferative activity of fluoroquinolone(rhodanine unsaturated ketone) amide derivatives

作　　者：高留州[1] 谢玉锁 闫强[1] 吴淑敏[1] 倪礼礼 赵辉[1] 黄文龙[2] 胡国强[1] 

机构地区：[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

出　　处：《药学学报》2015年第8期1008-1012,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(20872028;21072045);河南省高等学校重点科研项目基金资助项目(15A350004)

摘　　要：为发现新型抗肿瘤绕丹宁不饱和酮衍生物,以氟喹诺酮酰胺骨架作为载体,设计合成了氟喹诺酮(绕丹宁α,β-不饱和酮)酰胺类目标化合物5a^5r,其结构经元素分析、1H NMR、MS确证。采用MTT法评价了目标化合物对人肝癌Hep-3B细胞、人Capan-1胰腺癌细胞及人HL60白血病细胞的体外增值抑制活性。结果表明,18个目标化合物对3种实验癌细胞的抗增殖活性均显著高于母体环丙沙星1的活性,其中对Capan-1细胞的活性最强,尤其是芳杂环或苯环带有吸电子羧基及磺酰氨基类化合物的活性与对照抗肿瘤药物阿霉素相当。为此,氟喹诺酮(绕丹宁不饱和酮)酰胺衍生物是一类有发展前景的抗肿瘤活性先导物。To discover novel antitumor rhodanine unsaturated ketones, a series of fluoroquinolone （rhodanine a, fl-unsaturated ketone） amine derivatives （Sa-Sr） were designed and synthesized with fluoroquinolone amide scaffold as a carrier. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS. The in vitro anti-proliferative activity against Hep-3B, Capan-1 and HL60 cells was evaluated by MTT assay. The results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. The SAR revealed that some compounds carrying aromatic heterocyclic rings or phenyl attached to an electron-withdrawing carboxyl or sulfonamide substituent were comparable to or better than comparison doxorubicin against Capan-1 cells. As such, it suggests that fluoroquinolone （rhodanine α,β-unsaturated ketone） amines are promising leads for the development of novel antitumor fluoroquinolones or rhodanine analogues.

关 键 词：氟喹诺酮C-3酰胺 绕丹宁 不饱和酮 抗细胞增殖活性 

分 类 号：R916[医药卫生—药学]