Hydrotrope assisted green synthesis of dicoumarols and in silico and in vitro antibacterial, antioxidant and xanthine oxidase inhibition studies.

Aqueous hydrotrope has been employed for the first time to synthesize heteroaryl dicoumarols by condensation of 4-hydroxycoumarin and different heterocyclic aldehydes. This method is highly efficient and green, and the same aqueous hydrotropic solution can be used up to five times without any considerable loss of yield in the product. The synthesized compounds showed good antibacterial potential against Gram-positive ( Staphylococcus aureus / NTCC 0997 and B. oceanisediminis ) and Gram-negative ( Escherichia coli / D0157:H7 and E. coli rosetta ) bacterial strains using the Resazurin microtiter plate visual method. The MIC value of 312 µg/ml for compounds 3b , 3k and 3l for S. aureus while 39 µg/ml for compounds 3a , 3b and 3k for E. coli and 625 µg/ml for 3a and 3b for B. oceanisediminis was observed. The compounds were screened via computational methods like molecular docking studies and molecular dynamic simulations with PDB Id's 2W9S and 2EX6. Antioxidant activity was assessed using DPPH and H 2 O 2 assays. Five compounds with the best binding score in molecular docking with XO (PDB ID: 1FIQ) have been tested in an in-vitro study using an enzyme inhibition assay. Novel compound 3b gave the IC50 value of 0.28 µg/ml, comparable to the standard drug Allopurinol.Communicated by Ramaswamy H. Sarma.