title: A novel cytosporone 3-Heptyl-4,6-dihydroxy-3H-isobenzofuran-1-one: synthesis; toxicological, apoptotic and immunomodulatory properties; and potentiation of mutagenic damage.
abstract: BACKGROUND
  A large number of studies are attempting to identify alternative products from natural sources or synthesized compounds that effectively interact with cancer cells without causing adverse effects on healthy cells. Resorcinolic lipids are a class of bioactive compounds that possess anticancer activity and are able to interact with the lipid bilayer. Therefore, the objective of this study was to synthesize a novel resorcinolic lipid and test its biological proprieties.
  
  
  METHODS
  We aimed to synthesize a novel resorcinolic lipid belonging to the class of cytosporones, AMS049 (3-Heptyl-4,6-dihydroxy-3H-isobenzofuran-1-one) and to evaluate the toxicity of two concentrations of this lipid (7.5 and 10 mg/kg) by determining its genotoxic, mutagenic, immunomodulatory, and apoptotic effects, as well as any biochemical and histopathological alterations in mice treated with cyclophosphamide. The results were analyzed by ANOVA followed by the Tukey test A . level of significance of p < 0.05 was adopted.
  
  
  RESULTS
  The new cytosporone AMS049 was synthesized in only three steps and in satisfactory yields. The results indicate that the compound is neither genotoxic nor mutagenic and does not alter biochemical parameters. The histological alterations observed in the liver and kidneys did not compromise the function of these organs. Histology of the spleen suggested immunomodulation, although no changes were observed in splenic phagocytosis or differential blood cell count. The results also show that AMS049 potentiates the mutagenic effect of the chemotherapy drug cyclophosphamide and that the combination induces apoptosis.
  
  
  CONCLUSIONS
  These facts indicate a potential therapeutic application of this novel cytosporone as an important chemotherapeutic adjuvant.
authors.affiliation: Centro de Estudos em Células Tronco, Terapia Celular e Genética Toxicológica - CeTroGen, Hospital Universitário "Maria Aparecida Pedrossian" - HUMAP, Empresa Brasileira de Serviços Hospitalares - EBSERH, Campo Grande, MS, Brazil. rodrigo.oliveira@ufms.br.|Programa de Mestrado em Farmácia, Centro de Ciências Biológicas e da Saúde - CCBS, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil. rodrigo.oliveira@ufms.br.|Programa de Pós-graduação em Saúde e Desenvolvimento na Região Centro-Oeste, Faculdade de Medicina "Dr. Hélio Mandetta" - FAMED, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil. rodrigo.oliveira@ufms.br.
authors.forename: Rodrigo Juliano
authors.initials: RJ
authors.lastname: Oliveira
authors.affiliation: Centro de Estudos em Células Tronco, Terapia Celular e Genética Toxicológica - CeTroGen, Hospital Universitário "Maria Aparecida Pedrossian" - HUMAP, Empresa Brasileira de Serviços Hospitalares - EBSERH, Campo Grande, MS, Brazil. stephaniedynczuki@hotmail.com.|Programa de Mestrado em Farmácia, Centro de Ciências Biológicas e da Saúde - CCBS, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil. stephaniedynczuki@hotmail.com.
authors.forename: Stephanie Dynczuki
authors.initials: SD
authors.lastname: Navarro
authors.affiliation: Programa de Mestrado em Farmácia, Centro de Ciências Biológicas e da Saúde - CCBS, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil. denis.lima@ufms.br.|Programa de Pós-graduação em Química, Instituto de Química, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil. denis.lima@ufms.br.
authors.forename: Dênis Pires
authors.initials: DP
authors.lastname: de Lima
authors.affiliation: Programa de Pós-graduação em Química, Instituto de Química, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil. alisson_meza@hotmail.com.
authors.forename: Alisson
authors.initials: A
authors.lastname: Meza
authors.affiliation: Centro de Estudos em Células Tronco, Terapia Celular e Genética Toxicológica - CeTroGen, Hospital Universitário "Maria Aparecida Pedrossian" - HUMAP, Empresa Brasileira de Serviços Hospitalares - EBSERH, Campo Grande, MS, Brazil. joao_rpe@hotmail.com.|Programa de Pós-graduação em Saúde e Desenvolvimento na Região Centro-Oeste, Faculdade de Medicina "Dr. Hélio Mandetta" - FAMED, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil. joao_rpe@hotmail.com.
authors.forename: João Renato
authors.initials: JR
authors.lastname: Pesarini
authors.affiliation: Programa de Pós-graduação em Química, Instituto de Química, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil. robertogomes@ufgd.edu.br.|Faculdade de Ciências Exatas e Tecnologia - FACET, Universidade Federal da Grande Dourados - UFGD, Dourados, MS, Brazil. robertogomes@ufgd.edu.br.
authors.forename: Roberto
authors.initials: R
authors.lastname: da Silva Gomes
authors.affiliation: Programa de Pós-graduação em Química, Instituto de Química, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil. carol.karaziack@gmail.com.
authors.forename: Caroline Bilhar
authors.initials: CB
authors.lastname: Karaziack
authors.affiliation: Centro de Estudos em Células Tronco, Terapia Celular e Genética Toxicológica - CeTroGen, Hospital Universitário "Maria Aparecida Pedrossian" - HUMAP, Empresa Brasileira de Serviços Hospitalares - EBSERH, Campo Grande, MS, Brazil. mari.mauro@hotmail.com.|Programa de Doutorado em Biotecnologia e Biodiversidade - Rede Pró Centro-Oeste, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil. mari.mauro@hotmail.com.
authors.forename: Mariana
authors.initials: M
authors.lastname: de Oliveira Mauro
authors.affiliation: Centro de Ciências Biológicas e da Saúde - CCBS, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil. andrealclaura@gmail.com.
authors.forename: Andréa Luiza
authors.initials: AL
authors.lastname: Cunha-Laura
authors.affiliation: Centro de Ciências Biológicas e da Saúde - CCBS, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil. antonio.monreal@ufms.br.
authors.forename: Antônio Carlos Duenhas
authors.initials: AC
authors.lastname: Monreal
authors.affiliation: Departamento de Química, Universidade Federal do Espírito Santo - UFES, Vitória, ES, Brazil. wandersonromao@gmail.com.
authors.forename: Wanderson
authors.initials: W
authors.lastname: Romão
authors.affiliation: Departamento de Química, Universidade Federal do Espírito Santo - UFES, Vitória, ES, Brazil. vljuniorqui@gmail.com.
authors.forename: Valdemar Lacerda
authors.initials: VL
authors.lastname: Júnior
authors.affiliation: Programa de Mestrado em Farmácia, Centro de Ciências Biológicas e da Saúde - CCBS, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil. adilson.beatriz@ufms.br.|Programa de Pós-graduação em Química, Instituto de Química, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil. adilson.beatriz@ufms.br.
authors.forename: Adilson
authors.initials: A
authors.lastname: Beatriz
mesh_terms: D000818:Animals; D017209:Apoptosis; D001572:Benzofurans / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000494:pharmacology; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000494:pharmacology; D004357:Drug Synergism; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D013154:Spleen / Q000187:drug effects
chemical_list: D001572:Benzofurans; D007155:Immunologic Factors; D003520:Cyclophosphamide