thioacetazone and benzaldehyde

The complexity and duration of tuberculosis (TB) treatment contributes to the emergence of drug resistant tuberculosis (DR-TB) and drug-associated side effects. Alternate chemotherapeutic agents are needed to shorten the time and improve efficacy of current treatment. In this study, we have assessed the antitubercular activity of NSC19723, a benzaldehyde thiosemicarbazone molecule. NSC19723 is structurally similar to thiacetazone (TAC), a second-line anti-TB drug used to treat individuals with DR-TB. NSC19723 displayed better MIC values than TAC against Mycobacterium tuberculosis and Mycobacterium bovis BCG. In our checkerboard experiments, NSC19723 displayed better profiles than TAC in combination with known first-line and recently approved drugs. Mechanistic studies revealed that NSC19723 inhibits mycolic acid biosynthesis by targeting the HadABC complex. Computational studies revealed that the binding pocket of HadAB is similarly occupied by NSC19723 and TAC. NSC19723 also improved the efficacy of isoniazid in macrophages and mouse models of infection. Cumulatively, we have identified a benzaldehyde thiosemicarbazone scaffold that improved the activity of TB drugs in liquid cultures, macrophages, and mice.

Topics: Animals; Antitubercular Agents; BCG Vaccine; Benzaldehydes; Humans; Mice; Molecular Docking Simulation; Mycobacterium tuberculosis; Mycolic Acids; Thioacetazone; Thiosemicarbazones

Topics: Benzaldehydes; Copper; Ions; Oxidoreductases; Quinolines; Sulfonic Acids; Thioacetazone; Thiosemicarbazones

Topics: Benzaldehydes; Body Fluids; Female; Humans; Parity; Thioacetazone; Thiosemicarbazones; Urine

Topics: Benzaldehydes; Body Fluids; Thioacetazone; Thiosemicarbazones

Topics: Benzaldehydes; Body Fluids; Exudates and Transudates; Thioacetazone; Thiosemicarbazones