In vitro anti-mycobacterial activity of novel benzo(c)thiophene-1, 3-dione: A novel scaffold against Mycobacterium tuberculosis. (November 2020)

• Record Type: Journal Article
• Authors: Liu, Fang; Hu, Jinliang; Chang, Li; Jiang, Yongmei
• Is Part Of: Microbial pathogenesis. Volume 148(2020)
• Publication Date: 2020-11
• Subjects: Tuberculosis -- Drug resistance -- Synergism -- Cytotoxicity -- Benzo(c)thiophene-1, 3-dione; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2020.104466
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: Tuberculosis (TB) an infectious disease with very high mortality claims approximately 1.5 million lives and infects 2 billion people annually. The present study evaluated anti-tuberculosis activity of benzo( c )thiophene-1, 3-dione against Mycobacterial tuberculosis H37RV in vitro and in vivo in tuberculosis mice model. The MIC of benzo( c )thiophene-1, 3-dione, rifampicin and isoniazid were found to be 4.0, 2.0 and 1.0 μg/ml, respectively. Benzo( c )thiophene-1, 3-dione showed MIC in the range of 8–14 μg/ml against four drug-resistant isolates of M. tuberculosis and MBC 14 μg/ml against M. tuberculosis H37RV. Interaction of benzo( c )thiophene-1, 3-dione with rifampicin led to 2-fold increase in anti-TB activity whereas with isoniazid improvement showed 4-fold enhancement. Fractional inhibitor concentration index suggested additive interaction with rifampicin and synergism with isoniazid. Treatment with benzo( c )thiophene-1, 3-dione at 1X MIC indicated bacteriostatic activity whereas at 2X, 4X and 4X MIC doses significant reduction in M. tuberculosis load was observed. The benzo( c )thiophene-1, 3-dione administration to mice at doses of 5000 and 1000 mg/kg caused no changes in behaviour nor any death. Benzo( c )thiophene-1, 3-dione treatment of tuberculosis mice model effectively inhibited pulmonary CFU compared to model group. Data obtained from MTT assay showed negligible cytotoxicity of benzo( c )thiophene-1, 3-dione against CMMT, MB 157, CL-S1, normal breast cells in 5–320 μg/ml concentration range. Thus, benzo( c )thiophene-1, 3-dione exhibits promising anti-mycobacterial activity against Mycobacterium tuberculosis H37RV and other drug resistant strains . In Mycobacterium tuberculosis mice model benzo( c )thiophene-1, 3-dione significantly suppressed bacterial load and showed synergism with isoniazid. Therefore, benzo( c )thiophene-1, 3-dione has potential to be evaluated further for development of anti-tuberculosis treatment. Highlights: The MIC of benzo( c )thiophene-1, 3-dione was found to be 4.0 μg/ml. Its MIC against four drug-resistant isolates of M. tuberculosis is in the range of 8–14 μg/ml. The MBC against M. tuberculosis H37RV is found to be 14 μg/ml. Benzo( c )thiophene-1, 3-dione treatment of tuberculosis mice model effectively inhibited pulmonary CFU compared to model group.