Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Muriel Duflos is active.

Publication


Featured researches published by Muriel Duflos.


European Journal of Medicinal Chemistry | 2001

N-pyridinyl-indole-3-(alkyl)carboxamides and derivatives as potential systemic and topical inflammation inhibitors

Muriel Duflos; Marie-Renee Nourrisson; Jacques Brelet; Jacqueline Courant; Guillaume LeBaut; Nicole Grimaud; Jean-Yves Petit

N-substituted-(indol-3-yl)carboxamides 10-15 and alkanamides 16-18 were prepared starting from the corresponding acids and submitted to screening for evaluation of their anti-inflammatory activity. None of the considered carboxamides exhibited significant inhibitory effect in the carrageenin-induced rat paw oedema after oral administration of 0.1 mM x kg(-1); nevertheless introduction of an alkyl chain, leading to alkanamides 16-18, induced moderate to high activity: 46-95% inhibition. The efficacy of these compounds in the inhibition of topical inflammation was confirmed by measuring reduction of ear thickness in the acute tetradecanoyl phorbol acetate (TPA)-induced mouse ear swelling assay. Preliminary pharmacomodulation brought to the fore that toxic effects induced, at 0.4 mM x kg(-1), by N-(pyridin-4-yl)(indol-3-yl)propanamide (17) could be attenuated or suppressed by 5-fluorination or introduction of a methoxycarbonylborane moiety, leading to 18 and 21.


ACS Medicinal Chemistry Letters | 2013

Discovery of a Novel Broad-Spectrum Antifungal Agent Derived from Albaconazole

Rémi Guillon; Fabrice Pagniez; Carine Picot; Damien Hédou; Alain Tonnerre; Elizabeth Chosson; Muriel Duflos; Thierry Besson; Cédric Logé; Patrice Le Pape

Synthesis of a strict structural analogue of albaconazole in which the quinazolinone ring is fused by a thiazole moiety led to the discovery of a new triazole with broad-spectrum antifungal activity. Compound I exhibited high in vitro activity against pathogenic Candida species and filamentous fungi and showed preliminary in vivo antifungal efficacy in a mice model of systemic candidiasis.


Journal of Pharmacy and Pharmacology | 2001

Synthesis of N-Pyridinyl(methyl)-1,2-dihydro-4-hydroxy-2-oxoquinoline-3-carboxamides and analogues and their anti-inflammatory activity in mice and rats

X. Collin; J.-M. Robert; Muriel Duflos; Gaétane Wielgosz; G. Le Baut; C. Robin-Dubigeon; Nicole Grimaud; F. Lang; Jean-Yves Petit

The topical anti‐inflammatory activity of a series of N‐pyridinyl(methyl)1,2‐dihydro‐4‐hydroxy‐2‐oxoquinoline‐3‐carboxamides, analogues of roquinimex, has been evaluated by measuring their inhibitory effect in the phorbol myristate acetate (PMA)‐induced mouse ear swelling test, used as a screening test.


Journal of Enzyme Inhibition and Medicinal Chemistry | 2002

New N -pyridinyl(methyl)-indole-2- and 3-(Alkyl)carboxamides and Derivatives Acting as Systemic and Topical Inflammation Inhibitors

Anne Bretéché; Muriel Duflos; Alexandra Dassonville; Marie-Renee Nourrisson; Jacques Brelet; Guillaume Le Baut; Nicole Grimaud; Jean-Yves Petit

A series of novel N -substituted-(indol-2-yl)carboxamides (12 - 18) and (indol-3-alkyl)carboxamides (25 - 31) were synthesized and evaluated as inhibitors of the inflammation process. Pharmacomodulation at the level of the amidic nitrogen by incorporation of the previously described pharmacophoric moieties 6-aminolutidine, β -picolylamine, 4-aminopyridine and piperazine was investigated; only two compounds (12) and (31) exhibited significant (~40%) inhibitory effect in the carrageenan-induced rat paw edema after oral administration of a dose of 0.1 mM kg −1. Replacement of the indole core by indazole failed to increase activity. Incorporation of an alkyl chain spacer led to more efficient compounds (46 - 52) especially in the indolepropanamide sub-series. Determination of the efficiency of the most active compounds on topical inflammation, by measuring reduction of ear thickness in the acute tetradecanoyl phorbol acetate (TPA)-induced mouse ear swelling assay, confirmed the high potency of propanamides (49) and (51) after oral administration: ID50 =0.041 ± 0.013 and 0.042 ± 0.016 mM kg −1 respectively. The less toxic propanamide (51) exerted a high level of inhibitory activity after topical application of 2 × 100 μg/ear: 78 ± 2%.


European Journal of Medicinal Chemistry | 1994

Non-acidic antiinflammatory compounds II. Synthesis and activity of 6-amino-2,4-lutidine derivatives

Jean-Michel Robert; Sylvie Robert-Piessard; Muriel Duflos; G. Le Baut; E. N. Khettab; Nicole Grimaud; Jean-Yves Petit; Lucien Welin

Benzamides I, phenylalkanamides II and cinnamamides III are structurally related to the antiinflammatory N-(4,6-dimethylpyridin-2-yl)benzamide I. These were synthesized and the transformation of the 2-aminopyridine nucleus of benzamides I into a 2-imino-1,2-dihydropyridine structure (compounds IV) was also carried out. Of the 49 new derivatives, the 3-fluorobenzamide 9 was the most potent in the oral treatment of carrageenen-induced peripheral edema; IC50 = 12.2 mg·kg−1. It was 3 times as active as benzamide 1, but the latter nevertheless had a better therapeutic index (LD50/IC50) of 52 against 23. Benzamide 1, a non-acidic antiinflammatory compound devoid of any blocking activity on cyclooxygenase, markedly reduces the production of reactive oxygen species in rat peritoneal macrophages. This compound probably acts at the membrane, perhaps by interference with transmembrane events.


Journal of Enzyme Inhibition and Medicinal Chemistry | 2011

Synthesis and in vitro antifungal evaluation of 2-(2,4- difluorophenyl)-1-((1H-indol-3-ylmethyl)methylamino)-3- (1H-1,2,4-triazol-1-yl)propan-2-ols

Rémi Guillon; Cédric Logé; Fabrice Pagniez; Véronique Ferchaud-Roucher; Muriel Duflos; Carine Picot; Patrice Le Pape

We extended our previous studies based on the design of 1-[(1H-indol-5-ylmethyl)amino]-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-2-ols as antifungal agents toward the identification of new indol-3-ylmethylamino derivatives. The majority of these compounds exhibited antifungal activity against a Candida albicans strain (minimum inhibitory concentrations ranging from 199.0 to 381.0 ng/mL) suggesting an inhibition of 14α-demethylase by sterol analysis studies, but are weaker inhibitors compared to their indol-5-ylmethylamino analogs.


ChemMedChem | 2011

Design, Synthesis, and Biological Evaluation of 1-[(Biarylmethyl)methylamino]-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ols as Potent Antifungal Agents: New Insights into Structure–Activity Relationships

Rémi Guillon; Fabrice Pagniez; Charlotte Rambaud; Carine Picot; Muriel Duflos; Cédric Logé; Patrice Le Pape

We recently reported the design and synthesis of azole antifungal agents with a focus on modifications to the side chain appended to the propanol group. Herein we have identified a series of new 1‐[(biarylmethyl)methylamino] derivatives with broad‐spectrum antifungal activities against the most prevalent human pathogenic fungi (Candida spp. and Aspergillus fumigatus). Compounds containing a flexible benzylamine moiety were clearly shown to yield the best antifungal activities, without the need for a hydrogen‐bond acceptor substituent directly attached to the para position. We were also able to determine that selected compounds are able to overcome gene overexpression and point mutations that lead to reduced susceptibility or resistance against current treatments, such as fluconazole. As the minor differences observed with small structural modifications cannot be explain with only a three‐dimensional model of CYP51, adequate physicochemical parameters must be evaluated in terms of antifungal potency, bioavailability, and toxicity. Therefore, structure–activity relationship studies such as these reveal new insights for the development of future antifungal therapies.


ChemMedChem | 2011

Design, Synthesis, and in vitro Antifungal Activity of 1-((4- Substituted-benzyl)methylamino)-2-(2,4-difluorophenyl)-3- (1H-1,2,4-triazol-1-yl)propan-2-ols

Rémi Guillon; Fabrice Pagniez; Francis Giraud; Damien Crepin; Carine Picot; Marc Le Borgne; F. Morio; Muriel Duflos; Cédric Logé; Patrice Le Pape

As part of our studies focused on the design of 1‐[((hetero)aryl‐ and piperidinylmethyl)amino]‐2‐phenyl‐3‐(1H‐1,2,4‐triazol‐1‐yl)propan‐2‐ols as antifungal agents, we report the development of new extended benzylamine derivatives substituted at the para position by sulfonamide or retrosulfonamide groups linked to alkyl or aryl chains. These molecules have broad‐spectrum antifungal activities not only against Candida spp., including fluconazole‐resistant strains, but also against a filamentous species (A. fumigatus). Concerning fluconazole resistance, selected compounds exhibit the capacity to overcome CDR and ERG11 gene upregulation and to maintain antifungal activity despite a recognized critical CYP51 substitution in C. albicans isolates. Synthesis, investigation of the mechanism of action by sterol analysis in a C. albicans strain, and structure–activity relationships (SARs) are reported.


Journal of Enzyme Inhibition and Medicinal Chemistry | 2003

Potential Inhibitors of Angiogenesis. Part I: 3-(Imidazol-4(5)-ylmethylene)indolin-2-ones

Emmanuelle Braud; Muriel Duflos; Marie-Renee Nourrisson; Alain Tonnerre; Carine Picot; Guillaume Le Baut; Pierre Renard; Bruno Pfeiffer; Gordon Tucker

The synthesis and pharmacological evaluation of new 3-(imidazol-4(5)-ylmethylene)indolin-2-ones, analogues of SU-5416, are reported. The final compounds 20-51 were obtained by Knoevenagel coupling between the substituted indolin-2-ones 1-15 and either the formylimidazole derivatives 16-18 or 2-formyl-3,5-dimethylpyrrole 19. Methylation at the nitrogen atom of the indolin-2-one and/or imidazole moities was carried out in the presence of the couple NaH/DMF. A Mannich reaction afforded the 1-dimethylaminomethyl derivatives 43 and 48. The antiangiogenic activity of these compounds was evaluated in a three dimensional in vitro rat aortic ring assay. In this test, compound 20 induced a decrease of angiogenesis comparable to that observed with SU-5416; the vascular density indexes at 1 μM were 30±18 and 22±4 % of control, respectively. The compounds were also evaluated, in an independent manner, as inhibitors of the human EGF-receptor tyrosine kinase activity. As expected, only minor activities were observed with four compounds, out of thirty-one, exerting inhibitory effects in the range of 40-55 % at 10 μM concentration.


European Journal of Medicinal Chemistry | 2016

Novel 1,6-naphthyridin-2(1H)-ones as potential anticancer agents targeting Hsp90.

David Montoir; Sophie Barillé-Nion; Alain Tonnerre; Philippe Juin; Muriel Duflos; Marc-Antoine Bazin

Hsp90 is an ATP-dependent chaperone known to be overexpressed in many cancers. This way, Hsp90 is an important target for drug discovery. Novobiocin, an aminocoumarin antibiotic, was reported to inhibit Hsp90 targeting C-terminal domain, and showed anti-proliferative properties, leading to the development of new and more active compounds. Consequently, a new set of novobiocin analogs derived from 1,6-naphthyridin-2(1H)-one scaffold was designed, synthesized and evaluated against two breast cancer cell lines. Subsequently, cell cycle progression and apoptosis were conducted on best candidates, finally Western Blot analysis was performed to measure their ability to induce degradation of Hsp90 client proteins.

Collaboration


Dive into the Muriel Duflos's collaboration.

Top Co-Authors

Avatar

Pierre Renard

Centre national de la recherche scientifique

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge