Synthesis and evaluation of functionalized indoles as antimycobacterial and anticancer agents

被引：0
作者：
Gökçe Cihan-Üstündağ
Gültaze Çapan
机构：
[1] Istanbul University,Department of Pharmaceutical Chemistry, Faculty of Pharmacy
来源：
Molecular Diversity | 2012年 / 16卷
关键词：
Indole; Spirothiazolidinone; Antimycobacterial activity; Antitumor activity;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
A new series of 5-fluoro-N2-(cyclohexylidene)-3-phenyl-1H-indole-2-carbohydrazides (6a–6e) and their cyclization products 5-fluoro-N-(3-oxo-1-thia-4-azaspiro [4.5]dec-4-yl)-3-phenyl-1H-indole-2-carboxamides (7a–7e, 8a–8e) have been synthesized and evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv using the Microplate Alamar Blue Assay (MABA). Compounds showed moderate to good inhibitory activity at 6.25 μg/mL. Among them, 7b, 7d, 8b, and 8d were the most potent analogs with an inhibition range of 91–95 %. Additionally, compounds 6a, 7a, 7e, 8a, and 8e were subjected to the National Cancer Institute’s (NCI) in vitro disease-oriented antitumor screening to be evaluated for antitumor activity. 8e, the most potent compound examined, displayed broad spectrum antiproliferative activity with particular selectivity against four leukemia cell lines (CCRF-CEM, HL-60 (TB), K-562, and RPMI-8226) with log10GI50 values between −5.68 and −6.09.
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页码：525 / 539
页数：14
相关论文
共 151 条
[1]  
Corbett EL(2003)The growing burden of tuberculosis: global trends and interactions with the HIV epidemic Arch Intern Med 163 1009-1021
[2]  
Watt CJ(2003)The global situation of MDR-TB Tuberculosis 83 44-51
[3]  
Walker N(2000)Apoptosis in cancer Carcinogenesis 21 485-495
[4]  
Maher D(2005)The concept of synthetic lethality in the context of anticancer therapy Nat Rev Cancer 5 689-698
[5]  
Williams BG(1952)A new Streptomyces antibiotic J Am Chem Soc 74 2947-2948
[6]  
Raviglione MC(1952)Actithiazic acid. I. Microbiological studies Antibiot Chemother 2 399-408
[7]  
Dye C(1998)Synthesis and biological evaluations of 3-substituted indolin-2-ones: a novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases J Med Chem 41 2588-2603
[8]  
Espinal MA(2006)Antitumor activity of substituted E-3-(3,4,5-trimethoxybenzylidene)-1,3-dihydroindol-2-ones J Med Chem 49 6922-6924
[9]  
Lowe SW(2007)Synthesis and structure–antituberculosis activity relationship of 1H-indole-2,3-dione derivatives Bioorg Med Chem 15 5888-5904
[10]  
Lin AW(2009)A microwave-assisted facile regioselective Fischer indole synthesis and antitubercular evaluation of novel 2-aryl-3,4-dihydro-2H-thieno[3,2-b]indoles Bioorg Med Chem Lett 19 3006-3009
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