La synthèse et l'évaluation cytotoxicité de dérivées triazolic contre des lignes de cellule de mélanome B16 et une méthodologie étudient sur la synthèse d'éthers propargyl de leur correspondance propargyl des esters sans catalyseur et sous des irradiations à micro-ondes

Synthesis and Cytotoxicity evaluation of small 1,4 - triazolic derivatives against B16 melanoma cell lines and a methodolgy study on the synthesis of propargyl ethers from their corresponding propargyl esters without catalyst and under microwave irradiations

• Auteur / Autrice : Shiva Kalhor Monfared
• Direction : Christian Girard, Jean Herscovici
• Type : Thèse de doctorat
• Discipline(s) : Chimie Organique
• Date : Soutenance le 18/09/2014
• Etablissement(s) : Paris 6
• Ecole(s) doctorale(s) : École doctorale Chimie moléculaire de Paris Centre (Paris)
• Jury : Examinateurs / Examinatrices : G. Prestat, B. Vauzeilles, Sandrine Sagan, Valérie Beneteau, F. Chemla

Mots clés

Mots clés contrôlés

Triazoles

Propargyle -- Composés

Mots clés libres

Chimie médicinale

Réaction de cycloaddition d'Huisgen

Réaction de Bestmann-Ohira

Cellules lignées de B16 mélanomes

Réaction au micro-onde

Ethers propargyliques

Medicinal chemistry

Huisgen cycloaddiction reaction

Résumé

La chimie médicinale est l’application des techniques de recherche en chimie pour synthétiser les molécules pharmaceutiques. Au cours des premiers stades de développements de chimie médicinale, les scientistes ont été principalement concernés par l’isolement des agents médicinaux présents dans les plantes, mais aujourd’hui, ils sont également impliqués dans la création et la synthèse de nouveaux composés pharmaceutiques, parfois basées sur des mécanismes récemment découverts.

Medicinal chemistry is the application of chemical research techniques to the synthesis of pharmaceuticals. During this PhD project, we tried to synthesize small molecules based on terminal alkyne and propargyl alcohols. These molecules were prepared by departing from a simple aldehyde and by doing reactions like Bestmann-Ohira in order to prepare terminal alkynes or reaction with ethynylmagnesium bromide to prepare propargyl alcoholsB. These prepared small molecules were then subjected into the 1,3-dipolar Huisgen cycloaddition reaction in the presence of organic azides in order to prepare small triazolic derivatives. Cytotoxicity property of these small triazoles was then tested against B16 melanoma cell lines. Primary results showed some activities for some of our synthesized molecules that need more study like adding functionalities on the structure to improve their activities.In the last part of this dissertation, a methodology study on the synthesis of propargyl ethers from their corresponding propargyl esters under microwave irradiations has been described. To the best of our knowledge preparation of propargyl ethers from propargyl esters or nucleophilic substitution of propargyl esters in order to find propargyl ethers has been reported in the literature only by use of catalysts such as Lewis acids or metal complexes. The advantage of our method was the absence of such catalysts and the time of the reaction which was less than 1h in comparison with the reported synthesis. Synthesis of such molecules can also be interesting in the synthesis of natural products.