Novel trans-2,3-dihydrofuro[3,2-c]coumarins were synthesized and assessed for their inhibition potential against cysteine proteases: cathepsin B, H and L which are the possible targets for anticancer activity. In general, the coumarin derivatives were found to be exceptional inhibitors against this class of enzymes. On the basis of molecular modeling data and structure-activity relationships, their inhibition patterns are also discussed. The selectivity of designed compounds as inhibitors against cathepsins B, H and L was demonstrated by enzyme inhibition data. Enzyme kinetics investigations were also on par with in vitro studies when tested on HepG2 carcinoma cell line utilizing 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Possible protein-drug interactions responsible for potential inhibition are demonstrated using docking studies.
Keywords: Dihydrofuro-coumarins; HepG2 carcinoma; cathepsins B, H and L; enzyme-inhibitors.