目的 发现转化抗菌氟喹诺酮到抗肿瘤氟喹诺酮的有效途径。方法 氧氟沙星酰肼与芳香羧酸在三氯氧磷中缩环合到目标物2-氟喹诺酮-5-芳基-NFDE6二唑衍生物。用MTT方法评价目标化合物3对体外培养肿瘤细胞的生长抑制活性。结果 合成了10个新的目标化合物,体外均显示潜在的抗癌活性。结论 杂环用作羧基的等排体值得关注。
Abstract
ObjectiveTo discover an efficient route for the conversion of an antibacterial fluoroquinolone to an antitumor one. Methods Cyclo-condensation of ofloxacin hydrazide 2 with aromatic carboxylic acids in POCl3 gave the corresponding oxadiazole derivatives 3a-3j, and their antitumor activity was evaluated by MTT assay. Results Ten title compunds were synthesized and showed potential antitumor activity. Conclusion Heterocycles as isosteric replacement of carboxyl are warrant further development.
关键词
抗肿瘤氟喹诺酮 /
NFDE6二唑 /
生物等排体 /
抗肿瘤活性
{{custom_keyword}} /
Key words
antitumor fluoroquinolone /
oxadiazole /
bioisostere /
antitumor evaluation
{{custom_keyword}} /
中图分类号:
R914
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
GHOSE A K, HERBERTZ T, PIPPIN D A, et al. Knowledge-based characterization of similarity relationships in the human protein-tyrosine phosphatase family for rational inhibitor design . J Med Chem, 2008, 51(17):5149.
BAX B D, CHAN P F, EGGLESTON D S, et al. Type IIA topoisomerase inhibition by a new class of antibacterial agents . Nature, 2010, 466(7309):935-940.
CHOU L C, TSAI M T, HSU M H, et al. Design, synthesis, and preclinical evaluation of new 5,6-(or 6,7-) disubstituted-2-(fluorophenyl)quinolin-4-one derivatives as potent antitumor agents . J Med Chem, 2010, 53(22):8047-8058.
AZEMA J, GUIDETTI B, DEWELLE J, et al. 7-((4-Substituted)piperazin-1-yl) derivatives of ciprofloxacin:Synthesis and in vitro biological evaluation as potential antitumor agents . Bioorg Med Chem, 2009, 17(15):5396-5407.
HU G Q, ZHANG Z Q, WANG X, et al. Synthesis and antibacterial activity of fluoroquinolone C-3 acylhydrazones . Chin Pharm J(中国药学杂志), 2010, 45(11):867-870.
HU G Q, CHEN Y S, WANG G Q, et al. Synthesis of fluoroquinolone C-3 heterocycles, bis-oxadiazole methylsulfides and methiodides, and their antitumor activity. Chin Pharm J(中国药学杂志), 2012, 47(1):72-76.
HU G Q, YANG Y, YI L, et al. Design, synthesis and antitumor activity of C3/C3 bis-fluoro- quinolones cross-linked with triazolothiadiazole . Acta Pharm Sin B, 2011, 1(3):172-177.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
国家自然科学基金资助项目(20872028, 21072045);河南大学科研基金资助
{{custom_fund}}