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

  • Bioorg Med Chem. 2017 Feb 15;25(4):1364-1373. doi: 10.1016/j.bmc.2016.12.043.
Balagani Sathish Kumar  1 ,  Kusumoori Ravi  1 ,  Amit Kumar Verma  1 ,  Kaneez Fatima  1 ,  Mohammad Hasanain  2 ,  Arjun Singh  1 ,  Jayanta Sarkar  2 ,  Suaib Luqman  1 ,  Debabrata Chanda  1 ,  Arvind S Negi  3
Affiliations
  • 1. CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow 226015, U.P., India.
  • 2. CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, U.P., India.
  • 3. CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow 226015, U.P., India. Electronic address: [email protected].
PMID: 28094224 DOI: 10.1016/j.bmc.2016.12.043
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.

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