Valentin Duvauchelle
@umu.se
Post-doctoral fellow, Department of Chemistry
Umeå University, Anna Linusson Lab
RESEARCH, TEACHING, or OTHER INTERESTS
Chemistry, Organic Chemistry, Biochemistry
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Chaimae Majdi, Valentin Duvauchelle, Patrick Meffre, and Zohra Benfodda
Elsevier BV
Rayane Ghoteimi, Abdennour Braka, Céline Rodriguez, Emeline Cros‐Perrial, Valentin Duvauchelle, Jean‐Pierre Uttaro, Christophe Mathé, Christine Ménétrier‐Caux, Lars Petter Jordheim, Laurent Chaloin,et al.
Wiley
AbstractVarious series of 4,6‐biaryl‐2‐thiopyridine derivatives were synthesized and evaluated as potential ecto‐5′‐nucleotidase (CD73) inhibitors. Two synthetic routes were explored and the coupling of 4,6‐disubstituted 3‐cyano‐2‐chloro‐pyridines with selected thiols allowed us to explore the structural diversity. Somehow divergent results were obtained in biological assays on CD73 inhibition using either the purified recombinant protein or cell‐based assays, highlighting the difficulty to target protein‐protein interface on proteins existing as soluble and membrane‐bound forms. Among the 18 new derivatives obtained, three derivatives incorporating morpholino substituents on the 4,6‐biaryl‐2‐thiopyridine core were shown to be able to reverse the adenosine‐mediated immune suppression on human T cells. The higher blockade efficiency was observed for 2‐((3‐cyano‐4,6‐bis(4‐morpholinophenyl)pyridin‐2‐yl)thio)‐N‐(isoxazol‐3‐yl)acetamide (with total reversion at 100 μM) and methyl 2‐((3‐cyano‐4,6‐bis(4‐morpholinophenyl)pyridin‐2‐yl)thio)acetate (with partial reversion at 10 μM). Thus, this series of compounds illustrates a new chemotype of CD73 allosteric inhibitors.
Miyanou Rosales-Hurtado, Valentin Duvauchelle, David Bénimélis, Maya Ogawa-Okada, Naofumi Yamamoto, Patrick Meffre, Hendrik Szurmant, and Zohra Benfodda
Springer Science and Business Media LLC
Valentin Duvauchelle, Patrick Meffre, and Zohra Benfodda
Springer Science and Business Media LLC
Valentin Duvauchelle, Patrick Meffre, and Zohra Benfodda
Elsevier BV
Valentin Duvauchelle, David Bénimélis, Patrick Meffre, and Zohra Benfodda
MDPI AG
An original and effective approach for achieving trifluoromethyl hydroxyalkylation of 5-phenylthiophen-2-amine using α-trifluoromethyl ketones is described. In the last few years, reaction of Friedel-Crafts had been widely used to realize hydroxyalkylation on heterocycles such as indoles or thiophenes by means of Lewis acid as catalyst. Additionally, amine functions are rarely free when carbonyl reagents are used because of their tendency to form imines. This is the first time that a site-selective electrophilic aromatic substitution on C3 atom of an unprotected 5-phenylthiophen-2-amine moiety is reported. The liberty to allow reaction in neutral conditions between free amine is valuable in a synthesis pathway. The reaction proceeds smoothly using an atom-economical metal-and catalyst-free methodology in good to excellent yields. A mechanism similar to an electrophilic aromatic substitution has been proposed.
Valentin Duvauchelle, Chaimae Majdi, David Bénimélis, Catherine Dunyach-Remy, Patrick Meffre, and Zohra Benfodda
Frontiers Media SA
Infections caused by drug-resistant bacteria are a serious threat to human and global public health. Moreover, in recent years, very few antibiotics have been discovered and developed by pharmaceutical companies. Therefore, there is an urgent need to discover and develop new antibacterial agents to combat multidrug-resistant bacteria. In this study, two novel series of juglone/naphthazarin derivatives (43 compounds) were synthesized and evaluated for their antibacterial properties against various clinical and reference Gram-positive MSSA, clinical Gram-positive MRSA, and clinical and reference Gram-negative bacteria E. coli and P. aeruginosa. These strains are of clinical importance because they belong to ESKAPE pathogens. Compounds 3al, 5ag, and 3bg showed promising activity against clinical and reference MSSA (MIC: 1–8 µg/ml) and good efficacy against clinical MRSA (MIC: 2–8 µg/ml) strains. 5am and 3bm demonstrated better activity on both MSSA (MIC: 0.5 µg/ml) and MRSA (MIC: 2 µg/ml) strains. Their MICs were similar to those of cloxacillin against clinical MRSA strains. The synergistic effects of active compounds 3al, 5ag, 5am, 3bg, and 3bm were evaluated with reference antibiotics, and it was found that the antibiotic combination with 3bm efficiently enhanced the antimicrobial activity. Compound 3bm was found to restore the sensitivity of clinical MRSA to cloxacillin and enhanced the antibacterial activity of vancomycin when they were added together. In the presence of 3bm, the MIC values of vancomycin and cloxacillin were lowered up to 1/16th of the original MIC with an FIC index of 0.313. Moreover, compounds 3al, 5ag, 5am, 3bg, and 3bm did not present hemolytic activity on sheep red blood cells. In silico prediction of ADME profile parameter results for 3bm is promising and encouraging for further development.
Valentin Duvauchelle, Elsa Causse, Julien Michon, Patrick Rateau, Karine Weiss, Patrick Meffre, and Zohra Benfodda
MDPI AG
In response to the antimicrobial resistance issue, the World Health Organization developed and conducted a survey in 2015 dealing with habits, antibiotic use, awareness of appropriate use and sensitization to the issue of antibacterial resistance. In France, we conducted a similar survey to investigate the use of antibiotics and students’ perceptions of the antibiotic resistance risk. Our results indicated that antibiotics are moderately taken (42% in the last six months), but mistakes remain in appropriate practices and knowledge. Many people still believe that the body develops resistance to antibiotics and 24% responded that antibiotics can be stopped before the end of the treatment if they feel better. Furthermore, only 14% said antibiotics could be used to treat gonorrhea while 57% indicated that influenza could be treated with antibiotics. We looked at risk perception as well, and noticed that students in biology were more aware of risk (mean score = 48.87) and health consequences (mean score = 40.33) than mathematics students (mean score = 44.11 and 37.44). They were more aware of the threat, had a better understanding of antibiotic resistance and their denial of this risk was less significant (mean score = 27.04 against 23.81). However, the importance of providing a minimum level of knowledge to young students has been emphasized, regardless of the field of expertise.