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

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• 作者：Balagani Sathish Kumar^a ; Kusumoori Ravi^a ; Amit Kumar Verma^a ; Kaneez Fatima^a ; Mohammad Hasanain^b ; Arjun Singh^a ; Jayanta Sarkar^b ; Suaib Luqman^a ; Debabrata Chanda^a ; Arvind S. Negi^a ; ^{arvindcimap@rediffmail.com}
• 关键词：Naphthoquinones ; Synthesis ; Regioselective ; Anticancer ; Topoisomerase ; Acute oral toxicity
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：15 February 2017
• 年：2017
• 卷：25
• 期：4
• 页码：1364-1373
• 全文大小：1173 K
• 卷排序：25

文摘

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 = 5.2 μM) 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 1000 mg/kg oral dose.