Synthesis, antibacterial and antitubercular activities of benzimidazole bearing substituted 2-pyridone motifs

被引：63
作者：
Desai, N. C. [1 ]
Shihory, N. R. [1 ]
Kotadiya, G. M. [1 ]
Desai, Priyanka [1 ]
机构：
[1] Maharaja Krishnakumarsinhji Bhavnagar Univ, Div Med Chem, Dept Chem, Bhavnagar 364002, Gujarat, India
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 82卷
关键词：
Antibacterial activity; Antitubercular activity; Benzimidazole; Cytotoxicity; MABA assay; 2-Pyridone; MYCOBACTERIUM-TUBERCULOSIS; STAPHYLOCOCCUS-AUREUS; CYTOTOXIC ACTIVITIES; DERIVATIVES; AGENTS; INHIBITORS; ASSAY;
D O I：
10.1016/j.ejmech.2014.06.004
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of benzimidazole bearing 2-pyridones 5a-r were synthesized and evaluated for their in vitro antibacterial and antitubercular activity. Further, all compounds were examined for their cytotoxic study on VERO cell line and characterized by well-known spectral techniques. It was observed that the compounds 5h, 5i, 5k, 5q and 5r were found to possess significant broad spectrum antibacterial activity (12.5-100 mu g/mL of MIC), while compounds 5g-5i, 5k and 5l proved to be the most potent antitubercular activity in range of 2.76-20.4 mu M of MIC at low level of cytotoxicity, indicating good selectivity. From SAR studies, lipophilic profile of compounds was remarkably vital for antibacterial activity, while MIC values of antitubercular activity could not be directly correlated with lipophilicity. (C) 2014 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：480 / 489
页数：10
相关论文
共 38 条
[1]   Synthesis of 4-alkyl (aryl)-6-aryl-3-cyano-2(1H)-pyridinones and their 2-imino isosteres as nonsteroidal cardiotonic agents [J].
Abadi, A ;
Al-Deeb, O ;
Al-Afify, A ;
El-Kashef, H .
FARMACO, 1999, 54 (04) :195-201
[2]   Tuberculosis 2013:5 Drug-resistant tuberculosis: time for visionary political leadership [J].
Abubakar, Ibrahim ;
Zignol, Matteo ;
Falzon, Dennis ;
Raviglione, Mario ;
Ditiu, Lucica ;
Masham, Susan ;
Adetifa, Lfedayo ;
Ford, Nathan ;
Cox, Helen ;
Lawn, Stephen D. ;
Marais, Ben J. ;
McHugh, Timothy D. ;
Mwaba, Peter ;
Bates, Matthew ;
Lipman, Marc ;
Zijenah, Lynn ;
Logan, Simon ;
McNerney, Ruth ;
Zumla, Adam ;
Sarda, Krishna ;
Nahid, Payam ;
Hoelscher, Michael ;
Pletschette, Michel ;
Memish, Ziad A. ;
Kim, Peter ;
Hafner, Richard ;
Cole, Stewart ;
Migliori, Giovanni Battista ;
Maeurer, Markus ;
Schito, Marco ;
Zumla, Alimuddin .
LANCET INFECTIOUS DISEASES, 2013, 13 (06) :529-539
[3]   Synthesis and antiparasitic and antifungal evaluation of 2′-arylsubstituted-1H,1′H-[2,5′]bisbenzimidazolyl-5-carboxamidines [J].
Alp, Mehmet ;
Goker, Hakan ;
Brun, Reto ;
Yildiz, Sulhiye .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2009, 44 (05) :2002-2008
[4]   Synthesis and antitubercular activity of imidazo[2,1-b] thiazoles [J].
Andreani, A ;
Granaiola, M ;
Leoni, A ;
Locatelli, A ;
Morigi, R ;
Rambaldi, M .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2001, 36 (09) :743-746
[5]   Synthesis, physicochemical properties and antimicrobial activity of some new benzimidazole derivatives [J].
Ansari, K. F. ;
Lal, C. .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2009, 44 (10) :4028-4033
[6]   MRSA - the tip of the iceberg [J].
Appelbaum, PC .
CLINICAL MICROBIOLOGY AND INFECTION, 2006, 12 :3-10
[7]   Mycobacterium tuberculosis dihydrofolate reductase is a target for isoniazid [J].
Argyrou, A ;
Vetting, MW ;
Aladegbami, B ;
Blanchard, JS .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2006, 13 (05) :408-413
[8]  
Avinash P., 2008, Rasayan J. Chem, V1, P447
[9]   The therapeutic journey of benzimidazoles: A review [J].
Bansal, Yogita ;
Silakari, Om .
BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (21) :6208-6236
[10]   New bis(pyridyl)methane derivatives from 4-hydroxy-2-pyridones: synthesis and antitumoral activity [J].
Cocco, MT ;
Congiu, C ;
Onnis, V .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2003, 38 (01) :37-47
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