Synthesis of pharmacologically important naphthoquinones and anticancer activity of 2-benzyllawsone through DNA topoisomerase-II inhibition. Issue 4 (15th February 2017)

• Record Type: Journal Article
• Authors: Kumar, Balagani Sathish; Ravi, Kusumoori; Verma, Amit Kumar; Fatima, Kaneez; Hasanain, Mohammad; Singh, Arjun; Sarkar, Jayanta; Luqman, Suaib; Chanda, Debabrata; Negi, Arvind S.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 4(2017)
• Page Start: 1364
• Page End: 1373
• Publication Date: 2017-02-15
• Subjects: Naphthoquinones -- Synthesis -- Regioselective -- Anticancer -- Topoisomerase -- Acute oral toxicity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.12.043
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Simple, efficient and straight-forward syntheses of lawsone (1 ), lapachol (2 ), and β-lapachone (3b ) have been achieved. Lawsone derivative exhibited significant anticancer activity through induction of apoptosis through caspase pathway and topoisomerase-II inhibition. Abstract: 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. compound21a exhibited potential anticancer activity (IC50 = 5.2 μM) against FaDu cell line. Compound21a 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. Compound21a was found to be safe in Swiss albino mice up to 1000 mg/kg oral dose.