Quinonoid compounds via reactions of lawsone and 2-aminonaphthoquinone with α-bromonitroalkenes and nitroallylic acetates: Structural diversity by C-ring modification and cytotoxic evaluation against cancer cells

  • Eur J Med Chem. 2018 May 10:151:686-704. doi: 10.1016/j.ejmech.2018.03.079.
Thekke V Baiju  1 ,  Renata G Almeida  2 ,  Sudheesh T Sivanandan  1 ,  Carlos A de Simone  3 ,  Lucas M Brito  4 ,  Bruno C Cavalcanti  4 ,  Claudia Pessoa  4 ,  Irishi N N Namboothiri  5 ,  Eufrânio N da Silva Júnior  6
Affiliations
  • 1. Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, 400 076, India.
  • 2. Institute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, CEP, 31270-901, Belo Horizonte, MG, Brazil.
  • 3. Department of Physics and Informatics, Institute of Physics, University of São Paulo, São Carlos, 13560-160, SP, Brazil.
  • 4. Department of Physiology and Pharmacology, Federal University of Ceará, CEP, 60180-900, Fortaleza, CE, Brazil.
  • 5. Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, 400 076, India. Electronic address: [email protected].
  • 6. Institute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, CEP, 31270-901, Belo Horizonte, MG, Brazil. Electronic address: [email protected].
PMID: 29660689 DOI: 10.1016/j.ejmech.2018.03.079
Abstract

Morita-Baylis-Hillman acetates and α-bromonitroalkenes have been employed in cascade reactions with lawsone and 2-aminonaphthoquinone for the one-pot synthesis of heterocycle fused quinonoid compounds. The reactions reported here utilized the 1,3-binucleophilic potential of hydroxy- and aminonaphthoquinones and the 1,2/1,3-bielectrophilic potential of bromonitroalkenes and Morita-Baylis-Hillman acetates for the synthesis of pyrrole and furan fused naphthoquinones. The synthesized compounds were evaluated against HCT-116 (human colon carcinoma cells), PC3 (human prostate Cancer cells), HL-60 (human promyelocytic leukemia cells), SF295 (human glioblastoma cells) and NCI-H460 (human lung Cancer cells) and exhibited antitumor activity with IC50 values as low as < 2 μM. Selected compounds were also evaluated against OVCAR-8 (ovary), MX-1 (breast) and JURKAT (leukemia) cell lines. The cytotoxic potential of the Quinones evaluated was also assayed using non-tumor cells, exemplified by peripheral blood mononuclear (PBMC) and L929 cells.