Objective(s): Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a widespread infectious disease around the world. Early diagnosis is always important in order to avoid spreading. At present, many studies have confirmed that microRNA (miRNA) could be a useful tool for diagnosis. This study aimed to evaluate whether miRNAs could be regarded as a noninvasive diagnosis biomarker from sputum for pulmonary tuberculosis (PTB). Materials and Methods: The M. tuberculosis strain H37Rv was incubated and cultured with human macrophage line THP-1. The total RNA was extracted from the THP-1 cells for detection. Six increased expressions of miRNAs were selected by miRNA microarray chips and the miRNAs were confirmed by qRT-PCR in the M. tuberculosis infection cell model. At last, the efficiency of other methods was compared with using miRNA. Results: OnlymiR-155 showed abetter diagnostic value for PTB than the other five miRNAs to distinguish PTB from non-PTB, including pneumonia, lung cancer, and unexplained pulmonary nodules. Next, we detected and analyzed the results of 68 PTB patients and 122 non-PTB, the sensitivity and specificity of miR-155 detection was 94.1% and 87.7%, respectively. It was higher than sputum smear detection and anti-TB antibody detection. But slightly lower than ELISpot (97%, P=0.404). Interestingly, the ranking of sputum smear by Ziehl-Neelsen staining had positive correlation with the expression level of miR-155 in smear-positive sputum (R-2 =0.8443, P<0.05). Conclusion: Our research suggested that miR-155 may be an efficiency biomarker for active PTB diagnosis and bacteria-loads evaluation.

In a search of new potentially active antitubercular agents, here we have initiated with pharmacophore development, virtual screening and molecular docking studies to know flexible binding modes with target cavity of DprE1 enzyme. We have designed and synthesized 6-(trifluoromethyl)-N-(4-oxothiazolidin-3-yl)quinazoline-2-carboxamide derivatives and evaluated for antitubercular activity with specific DprE1 inhibition. The various steps have been completed by performing conden-sation of 6-(trifluoromethyl)quinazoline-2-carboxylic acid, aromatic aldehydes, methanol, Hydrazine hydrate,-(trifluoromethyl)quinazoline-2-carbohydrazide, 6-(trifluoromethyl)-N'-methylenequinazoline-2-carbohydrazide to obtained 6-(trifluoromethyl)-N-(4-oxothiazolidin-3-yl)quinazoline-2-carboxamide derivatives (3a-r) in better yields. Synthesized derivatives were characterized for their spectral anal-ysis. These compounds have been screened for their in vitro antitubercular activity against Mycobacte-rium tuberculosis H 37 RV. The compounds 3a (MIC-1.27 m M); 3e (MIC-1.12 m M); 3p (MIC-1.18 m M); and 3r (MIC-0.96 m M); exhibited notable in vitro antitubercular activity compare to the reference standard, Isoniazid. These four compounds were screened for DprE1 enzyme assay. Among those 3e and 3r has shown strong DprE1 inhibition, these compounds were substituted with nitro and hydroxyl group. (c) 2020 Elsevier B.V. All rights reserved.