α-Amylase and mycobacterium-TB H37Rv antagonistic efficacy of novel pyrazole-coumarin hybrids: an in vitro and in silico investigation.

The present investigation of minutiae to acquire structural information of the novel pyrazole-coumarin hybrids ( PC1-PC10 ) synthesized using ultrasound methods and characterized using different spectroscopic techniques: mass, 1 H-NMR, 13 C-NMR and IR spectroscopy, and theoretically explored using the DFT approach with a B3LYP/6-311G (d, p) basis set, and there in vitro, antagonistic efficacy against α-amylase and mycobacterium-TB H37Rv are described in this article. Pyrazole-coumarin hybrids ( PC1-PC10 ) showed α-amylase inhibition ranging from IC 50 (0.32-0.58 mM) when compared with acarbose (IC 50 = 0.34 mM). Similarly, Mycobacterium-TB H37Rv strain inhibition screening showed MIC values ranging from 62.5 to 1000 µg/mL when compared with rifampicin and isoniazid MIC = 0.25 and 0.20 µg/mL, respectively. Molecular docking and MD simulation studies were performed to determine the active sites and rationalize the activities of the active compounds. To investigate the binding conformation and dynamics responsible for their activity, the three most active compounds ( PC1, PC3 and PC6 ) were docked into the porcine pancreatic α-amylase active site (PDB ID: 1OSE ), and mycobacterium-TB H37Rv active site (PDB ID: 4TZK ). The binding interactions between PC1, PC3, and PC6 with α-amylase were like those responsible for inhibiting α-amylase by acarbose. Also, the mycobacterium-TB H37Rv inhibiting responsible residues were compared with standard isoniazid and rifampicin.Communicated by Ramaswamy H. Sarma.