Synthesis of Novel and Highly Functionalized 4-hydroxycoumarin Chalcone and their Pyrazoline Derivatives as Anti-Tuberculosis Agents

Condensation of ketones 1a-b with deferent aldehydes 2a-e gives chalcones 3a-j. These chalcones on cyclization with hydrazine hydrate/phenylhydrazine in the presence of glacial acetic acid give the corresponding pyrazolines 4a-t. The structures of new compounds have been established by extensive IR, NMR and X-ray crystallographic studies and were assayed for their antitubercular activity against M. tuberculosis H37Rv and INH resistant M. tuberculosis strains using agar dilution method. Among the both derivative compounds, 4-hydroxy-3-(5-(4-trifluoromethyl) phenyl)-4,5-dihydro-1H-pyrazol-3-yl-2H-chromen-2-one 4m produced the highest efficacy, exhibited >90% inhibition against MTB at a concentration of 4.94 mu M and against INHR-MTB at 14.78 mu M