7 results on '"Dumètre, Aurélien"'
Search Results
2. Discovery of a new antileishmanial hit in 8-nitroquinoline series.
- Author
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Paloque L, Verhaeghe P, Casanova M, Castera-Ducros C, Dumètre A, Mbatchi L, Hutter S, Kraiem-M'rabet M, Laget M, Remusat V, Rault S, Rathelot P, Azas N, and Vanelle P
- Subjects
- Animals, Antiprotozoal Agents chemical synthesis, Hep G2 Cells, Humans, Leishmania donovani growth & development, Life Cycle Stages drug effects, Mice, Nitroquinolines chemical synthesis, Antiprotozoal Agents chemistry, Antiprotozoal Agents pharmacology, Drug Discovery, Leishmania donovani drug effects, Nitroquinolines chemistry, Nitroquinolines pharmacology
- Abstract
A series of nitrated 2-substituted-quinolines was synthesized and evaluated in vitro toward Leishmania donovani promastigotes. In parallel, the in vitro cytotoxicity of these molecules was assessed on the murine J774 and human HepG2 cell lines. Thus, a very promising antileishmanial hit molecule was identified (compound 21), displaying an IC(50) value of 6.6 μM and CC(50) values ≥ 100 μM, conferring quite good selectivity index to this molecule, in comparison with 3 drug-compounds of reference (amphotericin B, miltefosine and pentamidine). Compound 21 also appears as an efficient in vitro antileishmanial molecule against both Leishmania infantum promastigotes and the intracellular L. donovani amastigotes (respective IC(50) = 7.6 and 6.5 μM). Moreover, hit quinoline 21 does not show neither significant antiplasmodial nor antitoxoplasmic in vitro activity and though, presents a selective antileishmanial activity. Finally, a structure-activity relationships study enabled to define precisely the antileishmanial pharmacophore based on this nitroquinoline scaffold: 2-hydroxy-8-nitroquinoline., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
3. Preparation and antiprotozoal evaluation of promising β-carboline alkaloids.
- Author
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Gellis A, Dumètre A, Lanzada G, Hutter S, Ollivier E, Vanelle P, and Azas N
- Subjects
- Alkaloids administration & dosage, Alkaloids chemistry, Amphotericin B pharmacology, Antiprotozoal Agents administration & dosage, Antiprotozoal Agents chemistry, Carbolines administration & dosage, Carbolines chemistry, Chloroquine pharmacology, Doxycycline pharmacology, Drug Resistance, Multiple, Humans, Inhibitory Concentration 50, Pentamidine pharmacology, Structure-Activity Relationship, Alkaloids pharmacology, Antiprotozoal Agents pharmacology, Carbolines pharmacology, Leishmania donovani drug effects, Plasmodium falciparum drug effects
- Abstract
The synthesis of β-carbolines and their in vitro antiplasmodial and antileishmanial activities were described herein. These molecules have also been studied concerning their in vitro cytotoxicity toward the human cell line THP1, in order to calculate their respective selectivity indexes (SI). Among the 20 tested molecules, four exhibited significant antiplasmodial activity on the W2 multi-resistant Plasmodium falciparum strain (0.7 < IC₅₀ < 1.7 μM), in comparison with two references drugs (chloroquine and doxycycline), and a low cytotoxicity. These β-carbolines were also evaluated concerning their in vitro antileshmanial activity on Leishmania donovani promastigotes, permitting to identify an antileshmanial hit compound, displaying quite promising activity (IC₅₀ = 6.1 μM) in comparison with amphotericin B and pentamidine chosen as reference drugs. Finally, structure-activity relationships were discussed, pointing out that molecules presenting a para-substituted phenyl moiety at position 1 of the β-carboline ring displayed the best biological profile., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
4. Synthesis and evaluation of monoamidoxime derivatives: toward new antileishmanial compounds.
- Author
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Paloque L, Bouhlel A, Curti C, Dumètre A, Verhaeghe P, Azas N, and Vanelle P
- Subjects
- Acetates chemistry, Amphotericin B pharmacology, Animals, Antiprotozoal Agents pharmacology, Cell Line, Inhibitory Concentration 50, Leishmania donovani growth & development, Macrophages drug effects, Macrophages parasitology, Mice, Microwaves, Organometallic Compounds chemistry, Oximes pharmacology, Pentamidine pharmacology, Structure-Activity Relationship, Antiprotozoal Agents chemical synthesis, Leishmania donovani drug effects, Life Cycle Stages drug effects, Oximes chemical synthesis
- Abstract
A new series of monoamidoxime derivatives was synthesized using manganese(III) acetate by microwave irradiation. Several amidoximes (27-31, 33, 38) showed valuable in vitro activities toward Leishmania donovani promastigotes, exhibiting IC(50) values between 5.21 and 7.89 μM. In parallel, the cytotoxicity of these compounds was evaluated on murine J774A.1 cells, revealing the corresponding selectivity index (SI). Among the 13 tested compounds, 4 monoamidoximes (27-30) exhibited an SI more than 20 times better than pentamidine. Moreover, monoamidoxime 28 (4-[5-Benzyl-3-(4-fluorophenylsulfonyl)-5-methyl-4,5-dihydrofuran-2-yl]-N'-hydroxybenzimidamide) is 40 times more selective than pentamidine, and 1.6 times more than amphotericin B, used as reference drug compounds., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
5. Synthesis and evaluation of original amidoximes as antileishmanial agents.
- Author
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Bouhlel A, Curti C, Dumètre A, Laget M, Crozet MD, Azas N, and Vanelle P
- Subjects
- Antiprotozoal Agents chemistry, Antiprotozoal Agents toxicity, Cell Line, Cyclization, Humans, Leishmania donovani drug effects, Manganese chemistry, Oxidation-Reduction, Oximes chemical synthesis, Oximes toxicity, Structure-Activity Relationship, Antiprotozoal Agents chemical synthesis, Oximes chemistry
- Abstract
An original series of amidoxime derivatives was synthesized using manganese(III) acetate, Buchwald-Hartwig and Heck reactions. Two amidoximes (39 and 52) showed interesting in vitro activities toward Leishmania donovani promastigotes, exhibiting 8.3 and 8.8 μM IC(50) values. Moreover, the cytotoxicity of these compounds was evaluated on human THP1 cells, giving access to the corresponding selectivity index. Among the 25 tested compounds, amidoximes 38 and 39 and diamidoximes 50 and 52 exhibited a better selectivity index than pentamidine used as a drug compound reference., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
6. Synthesis and antiprotozoal activity of 4-arylcoumarins.
- Author
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Pierson JT, Dumètre A, Hutter S, Delmas F, Laget M, Finet JP, Azas N, and Combes S
- Subjects
- 4-Hydroxycoumarins chemical synthesis, Amphotericin B pharmacology, Antiprotozoal Agents chemical synthesis, Cell Line, Cell Proliferation drug effects, Coumarins chemical synthesis, Coumarins chemistry, Coumarins pharmacology, Humans, Inhibitory Concentration 50, Molecular Structure, Palladium chemistry, 4-Hydroxycoumarins chemistry, 4-Hydroxycoumarins pharmacology, Antiprotozoal Agents pharmacology, Leishmania donovani drug effects, Plasmodium falciparum drug effects
- Abstract
A large series of 4-arylcoumarins was synthesized by Suzuki-Miyaura cross-coupling reaction and evaluated for antiprotozoal activity against Plasmodium falciparum and Leishmania donovani. Several compounds were found to strongly inhibit the proliferation of human cell line and/or parasites. The 4-(3,4-dimethoxyphenyl)-6,7-dimethoxycoumarin exhibit a potent activity on L. donovani amastigotes with a selectivity index (SI=265) twice than amphotericin B (SI=140)., (Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
7. Original quinazoline derivatives displaying antiplasmodial properties.
- Author
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Kabri Y, Azas N, Dumètre A, Hutter S, Laget M, Verhaeghe P, Gellis A, and Vanelle P
- Subjects
- Aniline Compounds chemistry, Animals, Antiprotozoal Agents toxicity, Cell Line, Drug Design, Humans, Inhibitory Concentration 50, Leishmania donovani drug effects, Phosphotransferases antagonists & inhibitors, Plasmodium falciparum enzymology, Quinazolines toxicity, Toxoplasma drug effects, Antiprotozoal Agents chemistry, Antiprotozoal Agents pharmacology, Plasmodium falciparum drug effects, Quinazolines chemistry, Quinazolines pharmacology
- Abstract
The multistep synthesis of new quinazoline-derived molecules and their in vitro antiplasmodial evaluation on the W2 chloroquino-resistant Plasmodium falciparum strain is described herein. These molecules have also been studied concerning their in vitro cytotoxicity toward two human cell lines (K652 and HepG2) in order to calculate their respective selectivity indexes (S.I.). Among the fourteen tested molecules, two exhibited both significant antiplasmodial activity (IC(50)=0.95 and 1.3 microM) and low toxicity (IC(50)>100 or 125 microM), compared with two reference drugs: chloroquine and doxycycline. The structure activity relationships establish that the molecular scaffold which exerts the best profile is the 6-nitro-2-(tosylmethyl)-N-(3-substituted-phenyl)-quinazolin-4-amine. The hit molecules were finally investigated regarding their potential action toward two other protozoa, Leishmania donovani and Toxoplasma gondii, showing that these molecules display a selective antiplasmodial activity., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
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