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

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.