In Vitro Anticancer Activity, Toxicity and Structure-Activity Relationships of Phyllostictine A, a Natural Oxazatricycloalkenone Produced by the Fungus Phyllosticta cirsii.

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Abstract

The in vitro anticancer activity and toxicity of phyllostictine A, a novel oxazatricycloalkenone recently isolatedfrom a plant-pathogenic fungus (Phyllosticta cirsii) was characterized in six normal and five cancer cell lines.Phyllostictine A displays in vitro growth-inhibitory activity both in normal and cancer cells without actualbioselectivity, while proliferating cells appear significantly more sensitive to phyllostictine A than nonproliferatingones. The main mechanism of action by which phyllostictine displays cytotoxic effects in cancercells does not seem to relate to a direct activation of apoptosis. In the same manner, phyllostictine A seems notto bind or bond with DNA as part of its mechanism of action. In contrast, phyllostictine A strongly reacts withGSH, which is a bionucleophile. The experimental data from the present study are in favor of a bondingprocess between GSH and phyllostictine A to form a complex though Michael attack at C=C bond at theacrylamide-like system. Considering the data obtained, two new hemisynthesized phyllostictine A derivativestogether with three other natural phyllostictines (B, C and D) were also tested in vitro in five cancer cell lines.Compared to phyllostictine A, the two derivatives displayed a higher, phyllostictines B and D a lower, andphyllostictine C an almost equal, growth-inhibitory activity, respectively. These results led us to proposepreliminary conclusions in terms of the structure-activity relationship (SAR) analyses for the anticanceractivity of phyllostictine A and its related compounds, at least in vitro.

Autore Pugliese

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  • Le Calvé B.; Lallemand B.; Perrone C.; Lenglet G.; Depauw S.; Van Goietsenoven G.; Mbury M.; Vurro M.; Herphelin F.; Andolfi A.; Zonno M.C.; Mathieu V.; Dufrasne F.; Van Antwerpen P.; Poumay Y.; David-Cordonnier M.H.; Evidente A.; Kiss R.

Titolo volume/Rivista

Toxicology and applied pharmacology

Anno di pubblicazione

2011

ISSN

0041-008X

ISBN

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Numero di citazioni Wos

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Settori ERC

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