Synthesis of novel 3-substituted coumarin derivatives by transition metal-catalyzed reactions and their antimicrobial and antitumoral evaluations

Title : Synthesis of novel 3-substituted coumarin derivatives by transition metal-catalyzed reactions and their antimicrobial and antitumoral evaluations

Abstract:

Coumarin has an important place in medicinal chemistry, as molecules incorporating the coumarin scaffold show a broad spectrum of pharmacological activities, including anticancer, antimicrobial, antiviral, antioxidant, anticoagulant, anti-inflammatory, and anti-enzymatic. The aim of our study was to synthesise new coumarin-based compounds by using transition metal-catalysed reactions and evaluate their antibacterial and antitumor potential.  A series of 7-hydroxycoumarin derivatives with aliphatic and aryl moiety attached directly at C-3 of coumarin ring and through the ethynyl or 1,2,3-triazole linker were prepared by Pd-catalysed or click reaction. The 3-substituted coumarin derivative bearing bistrifluoromethylphenyl at the C-4 position of 1,2,3-triazole showed strong and selective antiproliferative activity against cervix adenocarcinoma (HeLa) cells. The 7-hydroxy-4-methylcoumarin with a phenyl ring directly attached to coumarin at C-3 showed good potency against MRSA and VRE strains. The promising antiproliferative activity of coumarin derivative bearing 3,5-ditrifluoromethylphenyl substituent and antibacterial activity of coumarin derivative with aromatic moiety suggest that further enhancements could be obtained by structural optimisation of the coumarin core.

Audience take-away:

• Synthesis of 3-substituted coumarin derivatives by Pd-catalysed reaction will be presented.
• Synthesis by Cu(I) catalysed click reactions of coumarin derivatives substituted with 1,2,3-triazole ring will be presented.
• Results of antiproliferative and antimicrobial evaluations of novel coumarin derivatives will be presented and the influence of substituents on biological activity will be explained.

Biography:

Dr. Tatjana Gazivoda Kraljevic graduated in 2000 at the University of Zagreb, Croatia Faculty of Chemical Engineering and Technology and obtained her PhD in 2007 at the Faculty of Science. She has been working at the Faculty of Chemical Engineering and Technology since 2000, currently as vice-dean of education, teaching Organic Chemistry, Heterocyclic Chemistry, Modern Methods of Organic Synthesis, Organic Chemistry in Drug Development and Structure determination of Organic Compounds. Her research interest is focused on the development and synthesis of novel biologically active heterocyclc compounds such as purine isosters, pirimidine and coumarin derivatives by using transition metal catalysed reactions and the green synthetic approach.