Oxidative reactions of DNA commonly result in base modifications. Among the four DNA bases, guanine is the most susceptible to oxidation, and one of its main oxidized compounds, namely 8-oxo-7,8-dihydroguanine (8-oxoGua), has been extensively studied in terms of formation, repair, and mutagenicity. However, the latter modified purine base is readily subjected to further oxidation reactions which have recently become a matter of interest. Emphasis was placed in this work on the identification of the final singlet oxygen oxidation products of 8-oxoGua in single-stranded DNA. Oxaluric acid was found to be the predominant product of the reaction. Insights in the mechanistic pattern of oxaluric acid formation were gained from isotopic labeling experiments in association with mass spectrometry measurements. It was found that oxaluric acid is formed via an oxidized guanidinohydantoin intermediate, arising from the likely degradation of a transient 5-hydroperoxide. Two subsequent hydrolytic steps that are accompanied by the release of guanidine are likely to be involved in the formation of oxaluric acid.

Schistosomiasis is one of the world's greatly neglected tropical diseases, and its control is largely dependent on a single drug, praziquantel. Here, we report the in vitro effect of piplartine, an amide isolated from Piper tuberculatum (Piperaceae), on Schistosoma mansoni adult worms. A piplartine concentration of 15.8 μM reduced the motor activity of worms and caused their death within 24h in a RPMI 1640 medium. Similarly, the highest sub-lethal concentration of piplartine (6.3 μM) caused a 75% reduction in egg production in spite of coupling. Additionally, piplartine induced morphological changes on the tegument, and a quantitative analysis carried out by confocal microscopy revealed an extensive tegumental destruction and damage in the tubercles. This damage was dose-dependent in the range of 15.8-630.2 μM. At doses higher than 157.6 μM, piplartine induced morphological changes in the oral and ventral sucker regions of the worms. It is the first time that the schistosomicidal activity has been reported for piplartine.

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