Deprotometalation-iodolysis and computed CH acidity of 1,2,3- and 1,2,4-triazoles. Application to the synthesis of resveratrol analogues

International audience1-Aryl- and 2-aryl-1,2,3-triazoles were synthesized by N-arylation of the corresponding azoles using aryl iodides. The deprotometalations of 1-phenyl-1,2,3-triazole and -1,2,4-triazole were performed using a 2,2,6,6-tetramethylpiperidino-based mixed lithium-zinc combination and occurred at the most acidic site, affording by iodolysis the 5-substituted derivatives. Dideprotonation was noted from 1-(2-thienyl)-1,2,4-triazole by increasing the amount of base. From 2-phenyl-1,2,3-triazoles, and in particular from 2-(4-trifluoromethoxy)phenyl-1,2,3-triazole, reactions at the 4 position of the triazolyl, but also ortho to the triazolyl on the phenyl group, were observed. The results were analyzed with the help of the CH acidities of the substrates, determined in THF solution using the DFT B3LYP method. 4-Iodo-2-phenyl-1,2,3-triazole and 4-iodo-2-(2-iodophenyl)-1,2,3-triazole were next involved in Suzuki coupling reactions to furnish the corresponding 4-arylated and 4,2’-diarylated derivatives. When evaluated for biological activities, the latter (which are resveratrol analogues) showed moderate antibacterial activity and promising antiproliferative effect against MDA-MB-231 cell line

Study of the anti-bioadhesion activity of glass surfaces grafted with rare furanosidic carbohydrates

La biocontamination de surface par des microorganismes provoque d’importantes conséquences économiques et sanitaires. Les différents moyens de prévention mis en place de nos jours utilisent des composés biocides nocifs pour l’environnement et participent à la recrudescence de l’antibiorésistance des organismes pathogènes. Ces travaux de recherche étudient une approche alternative non-biocide et non-toxique. Elle consiste à inhiber l’adhésion microbienne en appliquant une couche de monofuranosides sur une surface. La conception des surfaces a débuté par les synthèses glycosidiques des furanosides cibles à partir du D-Glucose, D-Galactose et D- Mannose. Des homologues pyranosidiques, connus pour leur activité antiadhésive, ont été réalisés afin de comparer l’intérêt de la forme cyclique. Ces sucres ont ensuite été greffés par chimie click sur une surface de verre préfonctionnalisée et au travers d’un lien O-glycosidique ou S- glycosidique via un groupe triazole. Les surfaces résultantes ont été caractérisées à l’aide de la goniométrie et de la spectroscopie photoélectron par rayons X. Les études d’adhésion avec Pseudomonas aeruginosa ont révélé une activité anti-biodhésion des surfaces furanosidiques et pyranosidiques. Les interactions spécifiques et non-spécifiques ont été explorées gràce à l’adhésion de mutants déficiants en lectine et d’un modèle thermodynamique. Les résultats ont conclu que l’activité antiadhésive des monosaccharides était davantage liée aux propriétés physicochimiques des sucres plutôt qu’à des interactions biologiques.Surface biocontamination from microorganisms leads to serious economic and health issues. Nowadays, biocide compounds are mostly used as prevention. Nonetheless, they are known to be toxic for environment and to participate in the rise of the antibiotic resistance of pathogens. These research works examine a non-biocide and non-toxic approach. It is based on the inhibition of the microbial adhesion with a monofuranoside-functionalized surface. The development of surfaces was started with the glycosidic synthesis of target furanosides from D-Glucose, D-Galactose and D-Mannose. In order to compare the interest of the cyclic form, pyranosidic homologues, known for their anti-adhesive activity, were also achieved. The modified glycosides were then grafted to a prefunctionalized glass surface linked through an O-glycosidic or S-glycosidic via a triazole group. The resulted surfaces were characterized using goniometry and X-ray photoelectron spectroscopy. The adhesion studies with Pseudomonas aeruginosa have shown an anti-bioadhesion activity with furanosidic and glycosidic surfaces. Specific and non-specific interactions were explored through lectin deficient mutant strains and a thermodynamic approach. The anti-bioadhesive activity was concluded to depent more on the carbohydrate physicochemical properties, rather than the biological interactions

Étude de l'activité anti-bioadhésion de surfaces de verres greffées par des sucres furanosidiques rares

Surface biocontamination from microorganisms leads to serious economic and health issues. Nowadays, biocide compounds are mostly used as prevention. Nonetheless, they are known to be toxic for environment and to participate in the rise of the antibiotic resistance of pathogens. These research works examine a non-biocide and non-toxic approach. It is based on the inhibition of the microbial adhesion with a monofuranoside-functionalized surface. The development of surfaces was started with the glycosidic synthesis of target furanosides from D-Glucose, D-Galactose and D-Mannose. In order to compare the interest of the cyclic form, pyranosidic homologues, known for their anti-adhesive activity, were also achieved. The modified glycosides were then grafted to a prefunctionalized glass surface linked through an O-glycosidic or S-glycosidic via a triazole group. The resulted surfaces were characterized using goniometry and X-ray photoelectron spectroscopy. The adhesion studies with Pseudomonas aeruginosa have shown an anti-bioadhesion activity with furanosidic and glycosidic surfaces. Specific and non-specific interactions were explored through lectin deficient mutant strains and a thermodynamic approach. The anti-bioadhesive activity was concluded to depent more on the carbohydrate physicochemical properties, rather than the biological interactions.La biocontamination de surface par des microorganismes provoque d’importantes conséquences économiques et sanitaires. Les différents moyens de prévention mis en place de nos jours utilisent des composés biocides nocifs pour l’environnement et participent à la recrudescence de l’antibiorésistance des organismes pathogènes. Ces travaux de recherche étudient une approche alternative non-biocide et non-toxique. Elle consiste à inhiber l’adhésion microbienne en appliquant une couche de monofuranosides sur une surface. La conception des surfaces a débuté par les synthèses glycosidiques des furanosides cibles à partir du D-Glucose, D-Galactose et D- Mannose. Des homologues pyranosidiques, connus pour leur activité antiadhésive, ont été réalisés afin de comparer l’intérêt de la forme cyclique. Ces sucres ont ensuite été greffés par chimie click sur une surface de verre préfonctionnalisée et au travers d’un lien O-glycosidique ou S- glycosidique via un groupe triazole. Les surfaces résultantes ont été caractérisées à l’aide de la goniométrie et de la spectroscopie photoélectron par rayons X. Les études d’adhésion avec Pseudomonas aeruginosa ont révélé une activité anti-biodhésion des surfaces furanosidiques et pyranosidiques. Les interactions spécifiques et non-spécifiques ont été explorées gràce à l’adhésion de mutants déficiants en lectine et d’un modèle thermodynamique. Les résultats ont conclu que l’activité antiadhésive des monosaccharides était davantage liée aux propriétés physicochimiques des sucres plutôt qu’à des interactions biologiques

Pseudomonas aeruginosa resistance of monosaccharide-functionalized glass surfaces

International audienc

ROMP-based Glycopolymers with High Affinity for Mannose-Binding Lectins

Well-defined, highly reactive poly(norbornenyl azlactone)s of controlled length (number-average degree of polymerization DPn̅ = 10 to 1,000) were made by ring-opening metathesis polymerization (ROMP) of pure exo-norbornenyl azlactone. These were converted into glycopolymers using a facile postpolymerization modification (PPM) strategy based on click aminolysis of azlactone side groups by amino-functionalized glycosides. Pegylated mannoside, heptyl-mannoside, and pegylated glucoside were used in the PPM. Binding inhibition of the resulting glycopolymers was evaluated against a lectin panel (Bc2L-A, FimH, langerin, DC-SIGN, ConA). Inhibition profiles depended on the sugars and the degrees of polymerization. Glycopolymers from pegylated-mannoside-functionalized polynorbornene, with DPn̅ = 100, showed strong binding inhibition, with subnanomolar range inhibitory concentrations (IC50s). Polymers surpassed the inhibitory potential of their monovalent analogues by four to five orders of magnitude thanks to a multivalent (synergistic) effect. Sugar-functionalized poly(norbornenyl azlactone)s are therefore promising tools to study multivalent carbohydrate–lectin interactions and for applications against lectin-promoted bacterial/viral binding to host cells