02254nas a2200289   4500008004100000022001400041245010400055210006900159260010600228300001400334490000700348520119600355653001501551653001901566653001701585653001801602653002601620100003001646700002401676700001901700700001701719700001901736700002601755700003101781700002601812856012601838       2016                        eng d  a0960-894X00aNovel tetrazoloquinoline-rhodanine conjugates: highly efficient synthesis and biological evaluation0 aNovel tetrazoloquinolinerhodanine conjugates highly efficient sy  aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcMAY  a2278-22830 v263 a<p>In search of new active molecules against Mycobacterium tuberculosis (MTB) H37Ra and Mycobacterium bovis BCG, a small focused library of rhodanine incorporated tetrazoloquinoline has been efficiently synthesized by using [HDBU][HSO4] acidic ionic liquid. The compound 3c found to be promising inhibitor of MTB H37Ra and M. bovis BCG characterized by lower MIC values 4.5 and 2.0 mu g/mL, respectively. The active compounds were further tested for cytotoxicity against HeLa, THP-1, A549 and PANC-1 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Again, the synthesized compounds were found to have potential antifungal activity. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against a potential target Zmp1 enzyme of MTB H37Ra, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of in vitro and in silico study suggest that these compounds possess ideal structural requirement for the further development of novel therapeutic agents. (C) 2016 Elsevier Ltd. All rights reserved.</p>10aantifungal10aAntitubercular10aCytotoxicity10aDocking study10aRhodanine derivatives1 aSubhedar, Dnyaneshwar, D.1 aShaikh, Mubarak, H.1 aNawale, Laxman1 aYeware, Amar1 aSarkar, Dhiman1 aKhan, Firoz, A. Kalam1 aSangshetti, Jaiprakash, N.1 aShingate, Bapurao, B.  uhttp://library.ncl.res.in/content/novel-tetrazoloquinoline-rhodanine-conjugates-highly-efficient-synthesis-and-biological01952nas a2200145   4500008004100000245013800041210006900179260000800248300001000256490000800266520137300274100001701647700001901664856012301683       2018                        eng d00aNovel red fluorescence protein based microplate assay for drug screening against dormant mycobacterium tuberculosis by using paraffin0 aNovel red fluorescence protein based microplate assay for drug s  cMAY  a15-190 v1103 a<p>The hypoxia model of dormancy is widely used in drug screening programs to identify novel inhibitors against latent Mycobacterium tuberculosis disease. In earlier reported microplate assays, hypoxia was maintained by either sealing the microplate or shifting in an anaerobic chamber to develop dormant phenotype. In these assays, inhibitors were added during inoculation, which mainly represents the active stage inhibitors instead of the dormant ones. Herein, the culture was covered with paraffin to develop hypoxia condition and consequently providing the advantage of adding compounds at any stage during incubation of 96-well plate. The stable expression of the red fluorescent protein in the bacilli under both actively growing as well as dormant conditions also facilitate the reliable estimation of growth and inhibition kinetics of bacilli in medium. Furthermore, S/N ratio and Z' factor of this assay were found to be &gt; 27 and 0.91-0.94 respectively, which confirm the robustness of the protocol. This newly developed drug-screening assay offers an easy, inexpensive, safe and high throughput-screening tool to search novel antitubercular inhibitors against both active and dormant bacilli. The red fluorescent H37Ra strain is a suitable surrogate for the more virulent H37Rv strain, and thus this effort will help in combating latent tuberculosis.</p>1 aYeware, Amar1 aSarkar, Dhiman  uhttp://library.ncl.res.in/content/novel-red-fluorescence-protein-based-microplate-assay-drug-screening-against-dormant01958nas a2200181   4500008004100000022001400041245012100055210006900176260000900245300001000254490000700264520130300271100001901574700002001593700001701613700001901630856012701649       2021                        eng d  a2045-232200aNovel gene similar to nitrite reductase (NO forming) plays potentially important role in the latency of tuberculosis0 aNovel gene similar to nitrite reductase NO forming plays potenti  cOCT   a198130 v113 aThe development of the latent phenotype of Mycobacterium tuberculosis (Mtb) in the human lungs is the major hurdle to eradicate Tuberculosis. We recently reported that exposure to nitrite (10 mM) for six days under in vitro aerobic conditions completely transforms the bacilli into a viable but non-cultivable phenotype. Herein, we show that nitrite (beyond 5 mM) treated Mtb produces nitric oxide (NO) within the cell in a dose-dependent manner. Our search for the conserved sequence of NO synthesizing enzyme in the bacterial system identified MRA2164 and MRA0854 genes, of which the former was found to be significantly up regulated after nitrite exposure. In addition, the purified recombinant MRA2164 protein shows significant nitrite dependent NO synthesizing activity. The knockdown of the MRA2164 gene at mRNA level expression resulted in a significantly reduced NO level compared to the wild type bacilli with a simultaneous return of its replicative capability. Therefore, this study first time reports that nitrite induces dormancy in Mtb cells through induced expression of the MRA2164 gene and productions of NO as a mechanism for maintaining non-replicative stage in Mtb. This observation could help to control the Tuberculosis disease, especially the latent phenotype of the bacilli.1 aAgrawal, Sonia1 aGample, Suwarna1 aYeware, Amar1 aSarkar, Dhiman  uhttp://library.ncl.res.in/content/novel-gene-similar-nitrite-reductase-no-forming-plays-potentially-important-role-latency