Dissociation and electrooxidation of primaquine diphosphate as an approach to the study of anti-chagas prodrugs mechanism of action

La-Scalea, Mauro Aquiles; Chin, Chung Man; Cruz, Maria Soraida Silva; Serrano, Sı́lvia Helena Pires; Ferreira, Elizabeth Igne

doi:10.1016/s0302-4598(00)00093-3

Cited by 11 publications

(15 citation statements)

References 13 publications

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“…However, both PQ and its 2-methyl-PQ derivative were reported to be almost four times as effective as the control drug, nifurtimox, against the model disease in mice [58]. One of the hypotheses that advanced for the anti-trypanosomiasis activity of PQ and related 8AQs relies on the metabolic formation of free radicals that increase the oxidative stress in T. cruzi [59].…”

Section: 4 Against Trypanosomiasismentioning

confidence: 99%

Primaquine revisited six decades after its discovery

Vale¹,

Moreira²,

Gomes³

2009

European Journal of Medicinal Chemistry

321

308

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Section: 4 Against Trypanosomiasismentioning

confidence: 99%

Primaquine revisited six decades after its discovery

Vale¹,

Moreira²,

Gomes³

2009

European Journal of Medicinal Chemistry

321

308

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“…On the other hand, various QSARs have been reported on anticoccidial and/or antitoxoplasma lead compounds through computer-aided molecular design (Mc Farland et al, 1991;Mc Farland, 1992;Rhyu et al, 1995;Samarandra et al, 1998;Gonzalbes et al, 1999;Daunes et al, 2001;La-Scalea et al, 2001). The studies can be used as paradigms for our work.…”

Section: Specific Antecedents For the Present Researchmentioning

confidence: 99%

“…A research paper by La-Scalea et al (2001) describes the voltammetric behaviour of primaquine as support for the further understanding of the delivery and action mechanisms of its respective synthetic pro-drugs. There are several papers that describe the drug behaviour and in most cases a correlation between oxidation processes and pH is not found.…”

Section: Specific Antecedents For the Present Researchmentioning

confidence: 99%

Simple stochastic fingerprints towards mathematical modelling in biology and medicine. 1. The treatment of coccidiosis

Dı́az

Bastida

Castañedo

et al. 2004

Bulletin of Mathematical Biology

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We have developed a classification function that is capable of discriminating between anticoccidial and nonanticoccidial compounds with different structural patterns. For this purpose, we calculated the Markovian electron delocalization negentropies of several compounds. These molecular descriptors, which act as molecular fingerprints, are derived from an electronegativity-weighted stochastic matrix (1Pi). The method attempts to describe the delocalization of electrons with time during the process of molecule formation by considering the 3D environment of the atoms. Accordingly, the entropies of this random process are used as molecular descriptors. The present study involves a stochastic generalization of the original idea described by Kier, which concerned the use of molecular negentropies in QSAR. Linear discriminant analysis allowed us to fit the discriminant function. This function has given rise to a good classification of 82.35% (28 anticoccidials out of 34) and 91.8% of inactive compounds (56/61) in training series. An overall classification of 88.42% (84/95) was achieved. Validation of the model was carried out by means of an external predicting series and this gave a global predictability of 93.1%. Finally, we report the experimental assay (more than 95% of lesion control) of two compounds selected from a large data set through virtual screening. We conclude that the approach described here seems to be a promising 3D-QSAR tool based on the mathematical theory of stochastic processes.

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“…Nevertheless, its trypanomicidal activity was earlier demonstrated 7,8 . The mechanism of action of NF was found to be based on the inhibition of trypanothione reductase, an enzyme involved in the antioxidant system of the parasite, by means of reduction of the nitro group 9 . More recently, a novel NF derivative, hydroxymethylnitrofurazone (NFOH), was shown to present better trypanomicide activity and lower mutagenicity potential than NF 10 .…”

Section: Introductionmentioning

confidence: 99%