title: Evaluation of the cytotoxicity of structurally correlated p-menthane derivatives.
abstract: Compounds isolated from essential oils play an important role in the prevention and treatment of cancer. Monoterpenes are natural products, and the principal constituents of many essential oils. The aim of this study was to investigate the cytotoxic potential of p-menthane derivatives. Additionally, analogues of perillyl alcohol, a monoterpene with known anticancer activity, were evaluated to identify the molecular characteristics which contribute to their cytotoxicity, which was tested against OVCAR-8, HCT-116, and SF-295 human tumor cell lines, using the MTT assay. The results of this study showed that (-)-perillaldehyde 8,9-epoxide exhibited the highest percentage inhibition of cell proliferation (GI = 96.32%-99.89%). Perillyl alcohol exhibited high cytotoxic activity (90.92%-95.82%), while (+)-limonene 1,2-epoxide (GI = 58.48%-93.10%), (-)-perillaldehyde (GI = 59.28%-83.03%), and (-)-8-hydroxycarvotanacetone (GI = 61.59%-94.01%) showed intermediate activity. All of the compounds tested were less cytotoxic than perillyl alcohol, except (-)-perillaldehyde 8,9-epoxide (IC50 = 1.75-1.03 µL/mg). In general, replacement of C-C double bonds by epoxide groups in addition to the aldehyde group increases cytotoxicity. Furthermore, stereochemistry seems to play an important role in cytotoxicity. We have demonstrated the cytotoxic influence of chemical substituents on the p-menthane structure, and analogues of perillyl alcohol.
authors.affiliation: Departamento de Fisiologia, Universidade Federal de Sergipe, CEP 49100-000, São Cristóvão-SE, Brazil. lulisynalone@yahoo.com.br.
authors.forename: Luciana Nalone
authors.initials: LN
authors.lastname: Andrade
authors.affiliation: Departamento de Fisiologia, Universidade Federal de Sergipe, CEP 49100-000, São Cristóvão-SE, Brazil. tam_tamires@yahoo.com.br.
authors.forename: Tamires Cardoso
authors.initials: TC
authors.lastname: Lima
authors.affiliation: Departamento de Fisiologia, Universidade Federal de Sergipe, CEP 49100-000, São Cristóvão-SE, Brazil. ricardoamaral23@hotmail.com.
authors.forename: Ricardo Guimarães
authors.initials: RG
authors.lastname: Amaral
authors.affiliation: Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, CEP 60430-270, Fortaleza-SE, Brazil.
authors.forename: Cláudia do Ó
authors.initials: Cdo Ó
authors.lastname: Pessoa
authors.affiliation: Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, CEP 60430-270, Fortaleza-SE, Brazil. odorico@ufc.br.
authors.forename: Manoel Odorico de Moraes
authors.initials: MO
authors.lastname: Filho
authors.affiliation: Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, CEP 60430-270, Fortaleza-SE, Brazil. brunomsoares@gmail.com.
authors.forename: Bruno Marques
authors.initials: BM
authors.lastname: Soares
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, CP 5009, CEP 58051-970, João Pessoa-PB, Brazil. lazarofarm2@gmail.com.
authors.forename: Lázaro Gomes do
authors.initials: LG
authors.lastname: Nascimento
authors.affiliation: Farmácia, Universidade Federal de Sergipe, CEP 58051-970, Lagarto-SE, Brazil. a.acarvalho@yahoo.com.br.
authors.forename: Adriana Andrade
authors.initials: AA
authors.lastname: Carvalho
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, CP 5009, CEP 58051-970, João Pessoa-PB, Brazil. sousadam@yahoo.com.
authors.forename: Damião Pergentino
authors.initials: DP
authors.lastname: de Sousa
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013729:Terpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D013729:Terpenes
keywords: anticancer; antitumoral; cytotoxic activity; cytotoxicity; essential oils; monoterpenes; natural products; p-menthane; perillyl alcohol