title: Synthesis of pharmacologically important naphthoquinones and anticancer activity of 2-benzyllawsone through DNA 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. 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.
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow 226015, U.P., India.
authors.forename: Balagani Sathish
authors.initials: BS
authors.lastname: Kumar
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow 226015, U.P., India.
authors.forename: Kusumoori
authors.initials: K
authors.lastname: Ravi
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow 226015, U.P., India.
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Verma
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow 226015, U.P., India.
authors.forename: Kaneez
authors.initials: K
authors.lastname: Fatima
authors.affiliation: CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, U.P., India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hasanain
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow 226015, U.P., India.
authors.forename: Arjun
authors.initials: A
authors.lastname: Singh
authors.affiliation: CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, U.P., India.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Sarkar
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow 226015, U.P., India.
authors.forename: Suaib
authors.initials: S
authors.lastname: Luqman
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow 226015, U.P., India.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Chanda
authors.affiliation: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow 226015, U.P., India. Electronic address: arvindcimap@rediffmail.com.
authors.forename: Arvind S
authors.initials: AS
authors.lastname: Negi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II; C005090:lawsone
keywords: Acute oral toxicity; Anticancer; Naphthoquinones; Regioselective; Synthesis; Topoisomerase