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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

A novel cytosporone 3-Heptyl-4,6-dihydroxy-3H-isobenzofuran-1-one: synthesis; toxicological, apoptotic and immunomodulatory properties; and potentiation of mutagenic damage

Authors: Rodrigo Juliano Oliveira, Stephanie Dynczuki Navarro, Dênis Pires de Lima, Alisson Meza, João Renato Pesarini, Roberto da Silva Gomes, Caroline Bilhar Karaziack, Mariana de Oliveira Mauro, Andréa Luiza Cunha-Laura, Antônio Carlos Duenhas Monreal, Wanderson Romão, Valdemar Lacerda Júnior, Adilson Beatriz

Published in: BMC Cancer | Issue 1/2015

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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.

Conclusion

These facts indicate a potential therapeutic application of this novel cytosporone as an important chemotherapeutic adjuvant.
Appendix
Available only for authorised users
Footnotes
1
DBE (double bond equivalent) = c – h/2 + n/2 + 1, where c, h, and n are the number of carbon, hydrogen, and nitrogen atoms in the molecular formula, respectively.
 
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Metadata
Title
A novel cytosporone 3-Heptyl-4,6-dihydroxy-3H-isobenzofuran-1-one: synthesis; toxicological, apoptotic and immunomodulatory properties; and potentiation of mutagenic damage
Authors
Rodrigo Juliano Oliveira
Stephanie Dynczuki Navarro
Dênis Pires de Lima
Alisson Meza
João Renato Pesarini
Roberto da Silva Gomes
Caroline Bilhar Karaziack
Mariana de Oliveira Mauro
Andréa Luiza Cunha-Laura
Antônio Carlos Duenhas Monreal
Wanderson Romão
Valdemar Lacerda Júnior
Adilson Beatriz
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1532-2

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