Synthesis of Unsymmetrical Dicoumarol and Its Measurement as Inhibitor of NQO1

Abstract

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.