C-3噻唑并均三唑取代的培氟沙星衍生物的合成及抗肿瘤活性(Ⅸ)
Synthesis and antitumor activity of C-3 thiazolo [3, 2-b][1, 2, 4]triazole-substituted pefloxacin derivatives
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摘要: 为寻找抗肿瘤氟喹诺酮类化合物的新方法,用稠杂环核作为培氟沙星( 1 )C-3羧基的生物电子等排体,设计合成了12个新的噻唑并[3,2-b][1,2,4]三唑类目标化合物( 6a ~ 6l ),其结构经元素分析和光谱数据确证。选择SMMC-7721、L1210和HL60 3种肿瘤细胞株进行体外抗增殖活性实验,结果表明目标化合物的抗肿瘤活性高于先导化合物 1 和相应的开环中间体硫醚酮( 5a ~ 5l ),其中苯环上有羟基或氟原子取代的目标化合物对SMMC-7721肿瘤细胞显示出较强的活性。基于此,噻唑并均三唑稠杂环可作为氟喹诺酮C-3羧基的等排体用于抗肿瘤氟喹诺酮类化合物的设计。Abstract: To search for fluoroquinolones(FQs)with antitumor activity, the C-3 carboxylic acid group of pefloxacin( 1 )was replaced by fused heterocyclic core, and twelve novel thiazolo[3, 2-b][1, 2, 4]triazole heterocycles( 6a - 6l )were designed and synthesized. The structures of target compounds were characterized by elemental analysis and spectral data. The results of the in vitro antiproliferative effect on SMMC-7721, L1210 and HL60 cell lines showed that the title compounds exhibited more significant antitumor activity than both of the pefloxacin and the corresponding opening-ring intermediates( 5a - 5l ). Among them, the target compounds which possess a benzene ring bearing a hydroxyl group( 6e )or a fluorine atom( 6j )exhibited more potent antiproliferative effect on SMMC-7721 cells than other compounds. Therefore, the antitumor fluoroquinolones can be designed by replacing the C-3 carboxylic acid group of fluoroquinolones with the thiazolo [3, 2-b][1, 2, 4] triazole moiety.
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Keywords:
- fluoroquinolone /
- s-triazole /
- thiazole /
- thiazolotriazole /
- antitumor activity
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[1] Guo ZR.Strategy of molecular drug design:pharmacophore and scaffold hopping[J].Chin J Med Chem(中国药物化学杂志),2008,18(2):147-157. [2] Mugnaini C,Pasquini S,Corelli F.The 4-quinolone-3-carboxylic acid motif as a multivalent scaffold in medicinal chemistry[J].Curr Med Chem,2009,16(14):1746-1767. [3] Peng XM,Cai GX,Zhou CH.Recent developments in azole compounds as antibacterial and antifungal agents[J].Curr Top Med Chem,2013,13(16):1963-2010. [4] Sun YS,Xu QJ,Hou LL,et al. Synthesis antitumor activity of fluoroquinolone C-3 bioisosteres(IV): s-triazole-oxadiazole methylsulfide Mannich-base derivatives[J].J China Pharm Univ(中国药科大学学报),2014,45(1):39-42. [5] Xu QJ,Hou LL,Wu ZF,et al. Synthesis antitumor activity of fluoroquinolone C-3 bioisosteres(III): s-triazole-oxadiazole methylsulfide derivatives from pefloxacin[J].J China Pharm Univ(中国药科大学学报),2013,44(6):511-514. [6] You QD,Li ZY,Huang CH,et al. Discovery of a novel series of quinolone and naphthyridine derivatives as potential topoisomerase I inhibitors by scaffold modification[J].J Med Chem,2009,52(18):5649-5661. [7] Husain A, Rashid M, Mishra R, et al. Benzimidazole bearing oxadiazole and triazolo-thiadiazoles nucleus:design and synthesis as anticancer agents[J].Bioorg Med Chem Lett,2012,22(17):5438-5444. [8] Xie YS,Gao LZ,Yan Q,et al. Synthesis and antitumor activity of fluoroquinolone C-3 isosteres(VIII):s-triazole sulfide-one thiosemicarbazone derivatives from pefloxacin[J].J China Pharm Univ(中国药科大学学报),2015,46(4):416-420. [9] Xu QJ,Hou LL,Wu XK,et al. Synthesis and antitumor activity of ciprofloquinolone bis-(C3 /C7 hydrazone)s[J].J China Pharm Univ(中国药科大学学报),2013,44(1):35-38. -
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