A new group of tryptanthrin analogues were obtained and evaluated for their activity against
Mycobacterium tuberculosis H37Rv. Tryptanthrin is a known inhibitor of Mtb enoyl-acyl carrier protein
reductase (InhA) and modifications in its structure gave a group of 5H-[1,3,4]thiadiazolo[2,3-
b]quinazolin-5-one analogues with antimycobacterial various potency. The most active compound in the
series, 2-(propylthio)-5H-[1,3,4]thiadiazolo[2,3-b]quinazolin-5-one, exhibited the superior inhibition
activity (up to 100%) against mycobacterial growth at MIC 6.5 μg/mL and demonstrated a very low per
oral toxicity in animals falling under the category 5 according to GHS classification. Molecular modeling
studies were performed to investigate the binding mechanisms of the synthesized ligands with InhA.
Binding energies and non-covalent interactions stabilizing the ligand-receptor complexes were obtained
from the results of molecular docking.
Keywords: tryptanthrin, Mycobacterium tuberculosis, enoyl-acyl carrier protein reductase, drug design, enzyme models, thiadiazole, quinazolinone
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