Synthesis, biological evaluation and 3D QSAR study of 2,4-disubstituted quinolines as anti-tuberculosis agents

被引：24
作者：
Patel, Sanjay R. [1 ]
Gangwal, Rahul [2 ]
Sangamwar, Abhay T. [2 ]
Jain, Rahul [1 ]
机构：
[1] Natl Inst Pharmaceut Educ & Res, Dept Med Chem, Sas Nagar 160062, Punjab, India
[2] Natl Inst Pharmaceut Educ & Res, Dept Pharmacoinformat, Sas Nagar 160062, Punjab, India
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 93卷
关键词：
Tuberculosis; Ring-substituted quinolines; Synthesis; Homolytic free radical reaction; RING-SUBSTITUTED QUINOLINES; ALAMAR BLUE ASSAY; MYCOBACTERIUM-TUBERCULOSIS; ANTIMYCOBACTERIAL ACTIVITIES; 3D-QSAR; DERIVATIVES; ANALOGS; LEADS;
D O I：
10.1016/j.ejmech.2015.02.034
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The synthesis and anti-tuberculosis activity for three series of 2,4-disubstituted quinolines is reported. The synthesized compounds were evaluated for activity against M. tuberculosis H37Rv strain; most promising compounds from the series exhibited MIC99 values ranged between 3.125 and 6.25 mu/mL. None of the compounds exhibited cytotoxicity up to the highest test concentration of 200 mu/mL. To understand the relationship between structure and activity, a 3D-QSAR analysis has been carried out by Comparative Molecular Field Analysis (CoMFA). Atom-fit alignment provided the best model, and allowed prediction of the activity of molecules in the test sets leading to the rationalization of the relationship between structure and activity. (C) 2015 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：511 / 522
页数：12
相关论文
共 24 条
[1]   A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis [J].
Andries, K ;
Verhasselt, P ;
Guillemont, J ;
Göhlmann, HWH ;
Neefs, JM ;
Winkler, H ;
Van Gestel, J ;
Timmerman, P ;
Zhu, M ;
Lee, E ;
Williams, P ;
de Chaffoy, D ;
Huitric, E ;
Hoffner, S ;
Cambau, E ;
Truffot-Pernot, C ;
Lounis, N ;
Jarlier, V .
SCIENCE, 2005, 307 (5707) :223-227
[2]  
[Anonymous], 2013, Global tuberculosis report 2013
[3]   Therapeutic implications of drug interactions in the treatment of human immunodeficiency virus-related tuberculosis [J].
Burman, WJ ;
Gallicano, K ;
Peloquin, C .
CLINICAL INFECTIOUS DISEASES, 1999, 28 (03) :419-429
[4]   1,2,3,4,8,9,10,11-Octahydrobenzo[j]phenanthridine-7,12-diones as New Leads against Mycobacterium tuberculosis [J].
Cappoen, Davie ;
Claes, Pieter ;
Jacobs, Jan ;
Anthonissen, Roel ;
Mathys, Vanessa ;
Verschaeve, Luc ;
Huygen, Kris ;
De Kimpe, Norbert .
JOURNAL OF MEDICINAL CHEMISTRY, 2014, 57 (07) :2895-2907
[5]   Straightforward palladium-mediated synthesis and biological evaluation of benzo [j]phenanthridine-7,12-diones as anti-tuberculosis agents [J].
Cappoen, Davie ;
Jacobs, Jan ;
Tuyen Nguyen Van ;
Claessens, Sven ;
Diels, Gaston ;
Anthonissen, Roel ;
Einarsdottir, Thorbjorg ;
Fauville, Maryse ;
Verschaeve, Luc ;
Huygen, Kris ;
De Kimpe, Norbert .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2012, 48 :57-68
[6]   2,4-Dialkyl-8,9,10,11-tetrahydrobenzo[g]pyrimido[4,5-c]isoquinoline-1,3,7,12(2H,4H)-tetraones as new leads against Mycobacterium tuberculosis [J].
Claes, Pieter ;
Cappoen, Davie ;
Uythethofken, Cynthia ;
Jacobs, Jan ;
Mertens, Birgit ;
Mathys, Vanessa ;
Verschaeve, Luc ;
Huygen, Kris ;
De Kimpe, Norbert .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2014, 77 :409-421
[7]   Synthesis and antimycobacterial activity of analogues of the bioactive natural products sampangine and cleistopholine [J].
Claes, Pieter ;
Cappoen, Davie ;
Mbala, Blaise Mavinga ;
Jacobs, Jan ;
Mertens, Birgit ;
Mathys, Vanessa ;
Verschaeve, Luc ;
Huygen, Kris ;
De Kimpe, Norbert .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2013, 67 :98-110
[8]  
Collins Kalonji R., 2002, AIDS Reviews, V4, P165
[9]   Microplate Alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium [J].
Collins, LA ;
Franzblau, SG .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (05) :1004-1009
[10]   Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy [J].
Dean, GL ;
Edwards, SG ;
Ives, NJ ;
Matthews, G ;
Fox, EF ;
Navaratne, L ;
Fisher, M ;
Taylor, GP ;
Miller, R ;
Taylor, CB ;
de Ruiter, A ;
Pozniak, AL .
AIDS, 2002, 16 (01) :75-83
123