thiosemicarbazide and Tuberculosis

Original results are presented in the field of research that addresses the extension of the reaction of residue of acyl-thiosemicarbazide fixation on the structure of 5-nitrobenzimidazole by a sulphonic group. The aim of the study is the increase of new thiosemicarbazide derivatives' applicative potential in the field of biochemistry, with a wide range of medical applications. The newly obtained compounds were characterized by using elemental analysis and spectral analysis (FT-IR and

Topics: Antitubercular Agents; Humans; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Semicarbazides; Spectroscopy, Fourier Transform Infrared; Structure-Activity Relationship; Tuberculosis

Topics: Antitubercular Agents; Biofilms; Cell Line; Humans; Imidazoles; Macrophages; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Semicarbazides; Tuberculosis

We, herein, describe the synthesis of a series of novel aryl tethered 7,8-dihydroquinolin-5(6H)-ylidenehydrazinecarbothioamides 4a-v, which showed in vitro and in vivo antimycobacterial activity against Mycobacterium tuberculosis (Mtb) H37Rv. The intermediates dihydro-6H-quinolin-5-ones 3a-v were synthesized from β-enaminones, reacting with cyclochexane-1,3-dione/5,5-dimethylcyclohexane-1,3-dione and ammonium acetate using a modified Bohlmann-Rahtz reaction conditions. They were further reacted with thiosemicarbazide to give the respective hydrazine carbothioamides 4a-v. All the new analogues 4a-v, were characterized by their NMR and mass spectral data analysis. Among the twenty-two compounds screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC27294), two compounds, 4e and 4j, exhibited the highest inhibition with an MIC of 0.39 µg/mL. Compounds 4a, 4g, and 4k were found to inhibit Mtb at an MIC of 0.78 µg/mL. Hydrazinecarbothioamides 4a-k, exhibited enhanced activity than dihydroquinolinones 3a-k. The observed increase in potency provides a clear evidence that hydrazinecarbothioamide is a potential pharmacophore, collectively imparting synergistic effect in enhancing antitubercular activity of the dihydroquinolinone core. The in vivo (Zebra fish) antimycobacterial screening of the in vitro active molecules led to the identification of a hit compound, 4j, with significant activity in the Mtb nutrient starvation model (2.2-fold reduction). Docking studies of 4j showed a hydrogen bond with the P156 residue of the protein.

Topics: Animals; Antitubercular Agents; Disease Models, Animal; Drug Design; Humans; Hydrazines; Microbial Sensitivity Tests; Molecular Docking Simulation; Mycobacterium tuberculosis; Quinolones; Structure-Activity Relationship; Thioamides; Tuberculosis; Zebrafish

Topics: Antitubercular Agents; Semicarbazides; Thiosemicarbazones; Tuberculosis

Topics: In Vitro Techniques; Semicarbazides; Thiosemicarbazones; Tuberculosis

Topics: Semicarbazides; Sulfanilamide; Sulfanilamides; Sulfonamides; Tuberculosis