Synthesis of pharmacologically important naphthoquinones and anticancer activity of 2-benzyllawsone through DNA topoisomerase-II inhibition

Naphthoquinones are naturally occurring biologically active entities. Practical de novo syntheses of three naphthoquinones i.e. lawsone (1), lapachol (2), and β-lapachone (3b) have been achieved from commercially available starting Materials. The conversion of lapachol (2) to β-lapachone (3b) was achieved through p-TSA/Iodine/BF₃-etherate mediated regioselective cyclisation. Further, 2-alkyl and 2-benzyllawsone derivatives have been prepared as possible Anticancer agents. Four derivatives exhibited significant Anticancer activity and the best analogue i.e. compound 21a exhibited potential Anticancer activity (IC₅₀=5.2μM) against FaDu cell line. Compound 21a induced Apoptosis through activation of Caspase pathway and exerted cell cycle arrest at S phase in FaDU cells. It also exhibited significant topoisomerase-II inhibition activity. Compound 21a was found to be safe in Swiss albino mice up to 1000mg/kg oral dose.

Acute oral toxicity; Anticancer; Naphthoquinones; Regioselective; Synthesis; Topoisomerase.