CNRS Pharmacochemistry and Pharmacology for Development

Toulouse, France

CNRS Pharmacochemistry and Pharmacology for Development

Toulouse, France
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Ibrahim N.,CNRS Pharmacochemistry and Pharmacology for Development | Ibrahim N.,IRD Montpellier | Ibrahim H.,CNRS Pharmacochemistry and Pharmacology for Development | Ibrahim H.,IRD Montpellier | And 14 more authors.
International Journal of Pharmaceutics | Year: 2014

We recently showed that the indolone-N-oxides can be promising candidates for the treatment of chloroquine-resistant malaria. However, the in vivo assays have been hampered by the very poor aqueous solubility of these compounds resulting in poor and variable activity. Here, we describe the preparation, characterization and in vivo evaluation of biodegradable albumin-bound indolone-N-oxide nanoparticles. Nanoparticles were prepared by precipitation followed by high-pressure homogenization and characterized by photon correlation spectroscopy, transmission electron microscopy, differential scanning calorimetry and X-ray powder diffraction. The process was optimized to yield nanoparticles of controllable diameter with narrow size distribution suitable for intravenous administration, which guarantees direct drug contact with parasitized erythrocytes. Stable nanoparticles showed greatly enhanced dissolution rate (complete drug release within 30 min compared to 1.5% of pure drug) preserving the rapid antimalarial activity. The formulation achieved complete cure of Plasmodium berghei-infected mice at 25 mg/kg with parasitemia inhibition (99.1%) comparable to that of artesunate and chloroquine and was remarkably more effective in prolonging survival time and inhibiting recrudescence. In 'humanized' mice infected with Plasmodium falciparum, the same dose proved to be highly effective: with parasitemia reduced by 97.5% and the mean survival time prolonged. This formulation can help advance the preclinical trials of indolone-N-oxides. Albumin-bound nanoparticles represent a new strategic approach to use this most abundant plasma protein to target malaria-infected erythrocytes. © 2014 Elsevier B.V.


Odonne G.,University of the French West Indies and Guiana | Odonne G.,French National Center for Scientific Research | Berger F.,Institute Pasteur Of La Guyane | Stien D.,University of the French West Indies and Guiana | And 3 more authors.
Journal of Ethnopharmacology | Year: 2011

Ethnopharmacological relevance: Cutaneous leishmaniasis is a neglected disease with a high incidence in French Guiana, mainly in the middle and upper Oyapock basin, where Amerindian and some Brazilian people live. The main goals of this work were (i) to assess the knowledge about leishmaniasis in the different populations of the middle and upper Oyapock basin, (ii) to study the therapeutic strategies adopted by people affected by leishmaniasis and (iii) to document the use of phytotherapeutic remedies for leishmaniasis. Knowledge, attitudes and practices (K.A.P.) related to this disease and its treatments have been studied according to cultural group and geographical settlement. Within the Wayãpi group, the evolution of the knowledge of phytoremedies over the last 20 years has been characterised by literature-based comparisons. Materials and methods: A total of 144 questionnaires were administered in all the villages of the upper Oyapock and Camopi basins. Correspondence analyses were used for multivariate analysis. Plant species were identified at the Cayenne Herbarium (CAY). Results: The biomedical concept of leishmaniasis correlates well with the Teko and Wayãpi concepts of kalasapa and kalasapau. Although the vector of this disease was not correctly identified, the most commonly cited aetiology (74.5%) was vector-borne, and related epidemiological schemes correlate well with the one encountered in French Guiana. Theoretically and practically, health centres were the most commonly used resource for diagnostic in instances of leishmaniasis infection (65.9%), independently of the patient's cultural group, along with the use of pharmaceutical drugs (85.3%). Pharmaceuticals were commonly utilised despite the frequent (51.5%) use of phytotherapeutic remedies, alone or in combination with drugs. The most cited medicinal plant species for the treatment of leishmaniasis included Eleutherine bulbosa (Mill.) Urb. (Iridaceae, cited 14 times), Euterpe oleracea Mart. (Arecaceae, 9), Cecropia obtusa Trecul (Cecropiaceae, 8), Jatropha curcas L. (Euphorbiaceae, 7), Ceiba pentandra (L.) Gaertn. (Bombacaceae, 6) and Carica papaya L. (Caricaceae, 6). Multiple correspondence analyses demonstrated that the species used in leishmaniasis remedies are more prone to vary by the user's place of residence than by their cultural origin, which indicates that exchange of knowledge about leishmaniasis remedies has occurred across different cultural groups. Literature-based comparisons between the remedies for leishmaniasis used by the Wayãpi during the 1980s showed a striking evolution, both in terms of diversity of species and number of plants used. The large number of species shared with other Guianese groups argues for intercultural exchange and may explain the majority (57.1%) of the newly used species highlighted in our study. Conclusions: Leishmaniasis is a well-known disease in the studied area. Phytotherapeutic treatments are still in use, although they are not the main source of remedies, and should undergo pharmacological studies to evaluate their potential therapeutic value. © 2011 Elsevier Ireland Ltd. All rights reserved.


Le Lamer A.-C.,CNRS Pharmacochemistry and Pharmacology for Development | Ibrahim N.,CNRS Pharmacochemistry and Pharmacology for Development | Manjary F.,University of Toliary | Mallet-Ladeira S.,CNRS Institute of Chemistry | And 4 more authors.
Molecules | Year: 2013

Three new spermidine alkaloids and two known compounds were isolated from the leaves of Androya decaryi. Their structures were elucidated on the basis of their spectroscopic data (NMR and mass spectrometry), by X-Ray diffraction and by comparison with literature values. Evaluation of the in vitro antiplamosdial properties of the isolated compounds revealed they did not possess any significant activity. © 2013 by the authors.


Bertani S.,CNRS Pharmacochemistry and Pharmacology for Development | Pineau P.,Institute Pasteur Paris | Loli S.,Cayetano Heredia Peruvian University | Moura J.,Institute Of Recherche Pour Le Developpement | And 3 more authors.
PLoS ONE | Year: 2013

Background:In South America, the highest incidence of primary liver cancer is observed in Peru. However, national estimations on hepatocellular carcinoma incidence and mortality are approximated using aggregated data from surrounding countries. Thus, there is a lack of tangible information from Peru that impairs an accurate description of the local incidence, presentation, and outcomes of hepatocellular carcinoma. The present study attempts to fill this gap and assesses the clinical epidemiology of hepatocellular carcinoma in this country.Methods:A retrospective cohort study was conducted by analysing the medical charts of 1,541 patients with hepatocellular carcinoma admitted between 1997 and 2010 at the Peruvian national institute for cancer. The medical records including liver function, serologic status, and tumor pathology and stage were monitored. Statistical analyses were performed in order to characterize tumor presentation according to demographic features, risk factors, and regional origin.Results:Surprisingly, the age distribution of the patient population displayed bimodality corresponding to two distinct age-based subpopulations. While an older group was in keeping with the age range observed for hepatocellular carcinoma around the world, a younger population displayed an abnormally juvenile mean age of 25.5 years old. In addition, each subpopulation displayed age-specific pathophysiological and clinical characteristics.Conclusions:The analysis suggests two different age-specific natural histories of hepatocellular carcinoma in the Peruvian patient population. This otherwise unusual tumor process that is ongoing in younger patients leads to the hypothesis that there may be a Peru-endemic risk factor driving hepatocarcinogenesis in the local population. © 2013 Bertani et al.


Barea C.,University of Navarra | Pabon A.,University of Antioquia | Castillo D.,Cayetano Heredia Peruvian University | Zimic M.,Cayetano Heredia Peruvian University | And 7 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2011

Continuing with our efforts to identify new active compounds against malaria and leishmaniasis, 14 new 3-amino-1,4-di-N-oxide quinoxaline-2- carbonitrile derivatives were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against Plasmodium falciparum Colombian FCR-3 strain and Leishmania amazonensis strain MHOM/BR/76/LTB-012A. Further computational studies were carried out in order to analyze graphic SAR and ADME properties. The results obtained indicate that compounds with one halogenous group substituted in position 6 and 7 provide an efficient approach for further development of antimalarial and antileishmanial agents. In addition, interesting ADME properties were found. © 2011 Elsevier Ltd. All rights reserved.


Barea C.,University of Pamplona | Pabon A.,University of Antioquia | Galiano S.,University of Pamplona | Perez-Silanes S.,University of Pamplona | And 8 more authors.
Molecules | Year: 2012

Malaria and leishmaniasis are two of the World's most important tropical parasitic diseases. Thirteen new 2-cyano-3-(4-phenylpiperazine-1-carboxamido) quinoxaline 1,4-dioxide derivatives (CPCQs) were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against erythrocytic forms of Plasmodium falciparum and axenic forms of Leishmania infantum. Their toxicity against VERO cells (normal monkey kidney cells) was also assessed. None of the tested compounds was efficient against Plasmodium, but two of them showed good activity against Leishmania. Toxicity on VERO was correlated with leishmanicidal properties.


Festa C.,University of Naples Federico II | De Marino S.,University of Naples Federico II | D'Auria M.V.,University of Naples Federico II | Taglialatela-Scafati O.,University of Naples Federico II | And 3 more authors.
Tetrahedron | Year: 2013

Plakortides R-U, four new polyketide endoperoxides, have been isolated from the marine sponge Plakinastrella mamillaris. Their structures were elucidated on the basis of extensive NMR spectroscopic (1H and 13C, COSY, HSQC, HMBC, and ROESY) and MS analyses and by chemical methods. In addition, a new method for the unambiguous stereochemical elucidation of 3,6-disubstituted 1,2-dioxines, frequently isolated from Plakinidae sponges, is reported. Pharmacological analysis demonstrated that plakortide U is endowed with in vitro antiplasmodial activity against a chloroquine-resistant strain. © 2013 Elsevier Ltd. All rights reserved.


Magnaval J.-F.,University Paul Sabatier | Fillaux J.,Toulouse University Hospital Center | Fillaux J.,CNRS Pharmacochemistry and Pharmacology for Development | Fabre R.,University Paul Sabatier
Revue Francophone des Laboratoires | Year: 2014

Toxocariasis is a zoonotic helminthiasis due to the infection of humans with larvae of Toxocara sp. that are ascarid round worms. Only two species, Toxocara canis and Toxocara cati, are recognized so far as agents of the human disease. The laboratory diagnosis of the generalized forms of toxocariasis, namely visceral larva migrans and covert/common toxocariasis, is mostly serological, and relies upon ELISA using Toxo-cara canis excretory-secretory larval antigens. Any positive or border-line result should subsequently be checked by western blotting. Covert/common toxocariasis is mostly a benign frequent infection, so a large majority of infected subjects is asymptomatic or has very few symptoms, and therefore go undiagnosed. This form of toxocariasis usually is self-limiting and cured patients exhibit residual spécifie antibodies, so a positive serodiagnosis can be associated with any infectious or non-infectious disease. Considered apart from the clinical and laboratory context, such a positive result has no diagnostic value and should be only taken into account after the possible causes of any observed syndrome have been ruled out. Unlike what can be done for many other infections, the age of the présence of spécifie IgG cannot be assessed using the level of spécifie IgM. The détection of other classes of immunoglobulins - particularly IgE - or subclasses - IgG3 / IgG4 - or circulating Ag was proven to be unable to discriminate between active infections and the presence of residual antibodies. Currently, the diagnosis of an active covert toxocariasis relies upon indirect arguments, e.g., the presence of otherwise unexplained symptoms along with blood eosinophilia and/or elevated levels of eosinophil cationic protein, a situation which is far from ideal. © 2014 - Elsevier Masson SAS - Tous droits réservés.


PubMed | CNRS Pharmacochemistry and Pharmacology for Development
Type: Journal Article | Journal: PloS one | Year: 2013

In South America, the highest incidence of primary liver cancer is observed in Peru. However, national estimations on hepatocellular carcinoma incidence and mortality are approximated using aggregated data from surrounding countries. Thus, there is a lack of tangible information from Peru that impairs an accurate description of the local incidence, presentation, and outcomes of hepatocellular carcinoma. The present study attempts to fill this gap and assesses the clinical epidemiology of hepatocellular carcinoma in this country.A retrospective cohort study was conducted by analysing the medical charts of 1,541 patients with hepatocellular carcinoma admitted between 1997 and 2010 at the Peruvian national institute for cancer. The medical records including liver function, serologic status, and tumor pathology and stage were monitored. Statistical analyses were performed in order to characterize tumor presentation according to demographic features, risk factors, and regional origin.Surprisingly, the age distribution of the patient population displayed bimodality corresponding to two distinct age-based subpopulations. While an older group was in keeping with the age range observed for hepatocellular carcinoma around the world, a younger population displayed an abnormally juvenile mean age of 25.5 years old. In addition, each subpopulation displayed age-specific pathophysiological and clinical characteristics.The analysis suggests two different age-specific natural histories of hepatocellular carcinoma in the Peruvian patient population. This otherwise unusual tumor process that is ongoing in younger patients leads to the hypothesis that there may be a Peru-endemic risk factor driving hepatocarcinogenesis in the local population.


PubMed | CNRS Pharmacochemistry and Pharmacology for Development
Type: Journal Article | Journal: Planta medica | Year: 2012

Two new dihydrochalcones (1, 2), as well as eight known compounds, piperaduncin C (3), 2,6-dihydroxy-4-methoxydihydrochalcone (4), 4,2,6-trihydroxy-4-methoxydihydrochalcone (5), 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoic acid (6), 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoic acid (7), 4-hydroxy-3-(3-methyl-2-butenoyl)-5-(3-methyl-2-butenyl)-benzoic acid (8), 2,2-dimethyl-8-(3-methyl-2-butenyl)-2H-1-chromene-6-carboxylic acid (9), and 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxybenzoic acid (10) were isolated from the leaves of Piper dennisii Trelease (Piperaceae), using a bioassay-guided fractionation to determine their antileishmanial potential. Among them, compound 10 exhibited the best antileishmanial activity (IC50 = 20.8 M) against axenic amastigote forms of Leishmania amazonensis, with low cytotoxicity on murine macrophages. In the intracellular macrophage-infected model, compound 10 proved to be more active (IC50 = 4.2 M). The chemical structures of compounds 1-10 were established based on the analysis of the spectroscopic data.

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