Synthesis of Unsymmetrical Dicoumarol and Its Measurement as Inhibitor of NQO1
Unsymmetrical analogues of dicoumraol (1a-f) were synthesized using a simple two-steps protocol. The ‘half-way stage’ analogues of dicoumarol (4a-f) were synthesized and later reduced using NaBH4/LiBH4to give the unsymmetrical analogues of dicoumarol (1a-f). The structural identities of all the synthesized compounds were confirmed via melting point, mass spectrometry, IR and 1H NMR spectroscopy. Enzyme assay was carried out in order to determine their inhibitory potency towards NAD(P)H:oxidoreductase quinone 1 (NQO1) enzyme. Remarkably, all the compounds containing 2-hydroxyl-1-naphthyl ring (1a-c) with (IC50value ranges from 19 – 41 nM) are more effective as NQO1 inhibitors.