<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Claes, Pieter</style></author><author><style face="normal" font="default" size="100%">Davie Cappoen</style></author><author><style face="normal" font="default" size="100%">Uythethofken, Cynthia</style></author><author><style face="normal" font="default" size="100%">Jacobs, Jan</style></author><author><style face="normal" font="default" size="100%">Birgit Mertens</style></author><author><style face="normal" font="default" size="100%">Vanessa Mathys</style></author><author><style face="normal" font="default" size="100%">Luc Verschaeve</style></author><author><style face="normal" font="default" size="100%">Huygen, Kris</style></author><author><style face="normal" font="default" size="100%">De Kimpe, Norbert</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">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.</style></title><secondary-title><style face="normal" font="default" size="100%">Eur J Med Chem</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Eur J Med Chem</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Antitubercular Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Line</style></keyword><keyword><style  face="normal" font="default" size="100%">Dose-Response Relationship, Drug</style></keyword><keyword><style  face="normal" font="default" size="100%">Isoquinolines</style></keyword><keyword><style  face="normal" font="default" size="100%">Macrophages</style></keyword><keyword><style  face="normal" font="default" size="100%">mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Microbial Sensitivity Tests</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Structure</style></keyword><keyword><style  face="normal" font="default" size="100%">Mycobacterium tuberculosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Pyrimidinones</style></keyword><keyword><style  face="normal" font="default" size="100%">Quinones</style></keyword><keyword><style  face="normal" font="default" size="100%">Structure-Activity Relationship</style></keyword><keyword><style  face="normal" font="default" size="100%">Tuberculosis, Multidrug-Resistant</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2014 Apr 22</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">77</style></volume><pages><style face="normal" font="default" size="100%">409-21</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Given the re-emergence of tuberculosis in Europe and beyond, the search for novel bio-active compound classes against this disease is of utmost importance. As a result of a high intrinsic tolerance of the etiological agent, Mycobacterium tuberculosis, towards most antibiotics and xenobiotics, the search for such new compounds is far from trivial. Further exacerbated by the rapid generation and spread of drug resistant M. tuberculosis and fuelled by the HIV/AIDS pandemic, halting the tuberculosis epidemic is of paramount importance. As part of our program to design new 2-aza-anthraquinones with anti-mycobacterial activity, various dialkyltetrahydrobenzo[g]pyrimido[4,5-c]isoquinolinetetraones were designed and synthesised. The compounds were submitted to a biological evaluation in which the activity against M.tb H37Rv(lux) was observed, as well as the acute toxicity towards J774 A.1 macrophages. From these results, the selectivity index was calculated. Furthermore, the activity of the most promising compounds was further studied against a multi-drug resistant LAM-1 strain and against intracellular replicating M.tb. The study was further extended with a comet assay and a VITOTOX™ assay to investigate the possibility of observable genotoxic effects caused by these compounds.&lt;/p&gt;</style></abstract><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/24681334?dopt=Abstract</style></custom1></record></records></xml>