Biological Activity of Naphthoquinones Derivatives in the Search of Anticancer Lead Compounds
Alexandra G. Durán,
Nuria Chinchilla,
Ana M. Simonet,
M. Teresa Gutiérrez,
Jorge Bolívar,
Manuel M. Valdivia,
José M. G. Molinillo,
Francisco A. Macías
Affiliations
Alexandra G. Durán
Allelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus de Excelencia Internacional (ceiA3), School of Science, University of Cadiz, 11510 Puerto Real, Cádiz, Spain
Nuria Chinchilla
Allelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus de Excelencia Internacional (ceiA3), School of Science, University of Cadiz, 11510 Puerto Real, Cádiz, Spain
Ana M. Simonet
Allelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus de Excelencia Internacional (ceiA3), School of Science, University of Cadiz, 11510 Puerto Real, Cádiz, Spain
M. Teresa Gutiérrez
Department of Biomedicine, Biotechnology and Public Health-Biochemistry and Molecular Biology, Institute of Biomolecules (INBIO), University of Cádiz, República Saharaui 7, 11510 Puerto Real, Cádiz, Spain
Jorge Bolívar
Department of Biomedicine, Biotechnology and Public Health-Biochemistry and Molecular Biology, Institute of Biomolecules (INBIO), University of Cádiz, República Saharaui 7, 11510 Puerto Real, Cádiz, Spain
Manuel M. Valdivia
Department of Biomedicine, Biotechnology and Public Health-Biochemistry and Molecular Biology, Institute of Biomolecules (INBIO), University of Cádiz, República Saharaui 7, 11510 Puerto Real, Cádiz, Spain
José M. G. Molinillo
Allelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus de Excelencia Internacional (ceiA3), School of Science, University of Cadiz, 11510 Puerto Real, Cádiz, Spain
Francisco A. Macías
Allelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus de Excelencia Internacional (ceiA3), School of Science, University of Cadiz, 11510 Puerto Real, Cádiz, Spain
Naphthoquinones are a valuable source of secondary metabolites that are well known for their dye properties since ancient times. A wide range of biological activities have been described highlighting their cytotoxic activity, gaining the attention of researchers in recent years. In addition, it is also worth mentioning that many anticancer drugs possess a naphthoquinone backbone in their structure. Considering this background, the work described herein reports the evaluation of the cytotoxicity of different acyl and alkyl derivatives from juglone and lawsone that showed the best activity results from a etiolated wheat coleoptile bioassay. This bioassay is rapid, highly sensitive to a wide spectrum of activities, and is a powerful tool for detecting biologically active natural products. A preliminary cell viability bioassay was performed on cervix carcinoma (HeLa) cells for 24 h. The most promising compounds were further tested for apoptosis on different tumoral (IGROV-1 and SK-MEL-28) and non-tumoral (HEK-293) cell lines by flow cytometry. Results reveal that derivatives from lawsone (particularly derivative 4) were more cytotoxic on tumoral than in non-tumoral cells, showing similar results to those obtained with of etoposide, which is used as a positive control for apoptotic cell death. These findings encourage further studies on the development of new anticancer drugs for more directed therapies and reduced side effects with naphthoquinone skeleton.
