Synthetic Naphthoquinone Derivatives as Anticancer Agents in Ovarian Cancer: Cytotoxicity Assay and Investigation of Possible Biological Mechanisms Action |
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| Authors: | Renata Dalmaschio Daltoé Leticia Batista Azevedo Rangel Maicon Delarmelina Klesia Pirola Madeira Marcella Leite Porto Silvana Santos Meirelles Isabella dos Santos Guimarães Éclair Venturini Filho Alan Reinke Pereira Rafael de Queiroz Ferreira Gabriel Fernandes Souza dos Santos Izabela de França Schaffel José Walkimar de Mesquita Carneiro Artur M. S. Silva Sandro José Greco |
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| Affiliation: | 1. Pharmaceutical Sciences Department, Federal University of Espirito Santo, Vitória, Espírito Santo, 29047-105 Brazil;2. School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT United Kingdom;3. Pharmacy and Nutrition Department, Federal University of Espírito Santo, Alegre, Espírito Santo, 29500-000 Brazil;4. Federal Institute of Education, Science and Technology (IFES), Vila Velha, Espírito Santo, 29106-010 Brazil;5. Phisiological Sciences Department, Federal University of Espirito Santo, Vitória, Espírito Santo, 29047-105 Brazil;6. National Cancer Institute (INCA), Rio de Janeiro, 20230-130 Brazil;7. Chemistry Department, Federal University of Espírito Santo, Vitória, Espírito Santo, 29075-910 Brazil;8. Chemistry Institute, Fluminense Federal University, Niterói, Rio de Janeiro, 24020-141 Brazil;9. REQUIMTE & Department of Chemistry, University of Aveiro, Aveiro, 3810-193 Portugal |
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| Abstract: | In this study, eight naphthoquinone derivatives were synthesized in yields ranging from 52 to 96% using easy, fast, and low-cost methodologies. All naphthoquinone derivatives were screened for their in vitro anti-proliferative activities against OVCA A2780 cancer cell lines. Amongst all analysed compounds, derivatives 3 – 5 presented the most prominent cytotoxic potential. Naphthoquinones 3 and 4 , bearing sulfur-containing groups, were identified as having high potential for ROS production, in particular the superoxide anion. Furthermore, 3 and 4 compounds caused a decrease in the cell population in G0/G1 and induced more than 90% of the cell population to apoptosis. Compound 5 did not act in any of these processes. Finally, compounds 3 – 5 were tested for their inhibitory ability against PI3K and MAPK. Compounds 3 and 4 do not inhibit the PI3K enzyme. On the other hand, the naphthoquinone-polyphenol 5 was only able to inhibit the percentage of cells expressing pERK. |
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| Keywords: | naphthoquinone anticancer activity ovarian cancer |
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