Synthesis of Coumarin-pyrazoline hybrids: Anti-tubercular Activity and Molecular Docking Study on DAPA Synthase

Biotin as a vitamin, is involved in the growth of M. tb. Inhibiting DAPA synthase enzyme collapses the biosynthetic pathway, and leads to inhibition of biotin formation. Continuing a previously reported synthesis method, we explored 5-(aryl/heteroaryl)-3-(2-oxo-2H-chromen-3-yl)-4, 5-dihydro-1H-pyrazole-1-carboxamide for its novel anti-tb activity against TB strain H37Rv. This study demonstrates that new compounds have potential anti-tubercular activity, providing new insights for targeting the DAPA synthase enzyme (PDB ID - 4W1W). The designed compounds have shown hydrogen and hydrophobic binding interactions with active sites like ARG400, TYR25, PHE402, and TRP64. The compounds 3B and 3C have shown MIC at 3.12 µg/ml, possibly because of the methoxy group, an electron-donating group. Other compounds with electron-donating groups, such as 2,4-dichloro, 3,4-dichloro, 2-chloro-6-fluoro, and hydroxyl-containing derivatives, demonstrated promising in-vitro activity at minimum inhibitory concentration 6.25 µg/ml. Other than phenyl-substituted derivatives few unsubstituted, thiophene, and naphthalene, derivatives also displayed MIC at 6.25µg/ml against the Mtb strain.