Coumarin derivatives are an important group of biologically active compounds that have found a wide range of application in pharmacy and medicine. For this reason, their extraction from plants, as well as the synthesis in laboratories have been increased lately. Many studies have been conducted and various coumarins shown different biological activities such as antibacterial, antifungal, anti-inflammatory, anticoagulant, antioxidant, anticancer, anti-HIV and much more. Coumarins can also act as enzyme inhibitors. It has been proven that coumarins inhibit many enzymes, including lipoxygenases. Lipoxygenases are iron-containing enzymes that convert polyunsaturated fatty acids into biologically active compounds involved in the inflammatory and immune responses. Sometimes it is necessary to inhibit those enzymes to avoid adverse reactions in plants and animals as well as in humans. During compounds synthesis in laboratory, it is important to minimize environmental contamination. Therefore, use of deep eutectic solvents is preferable, due to their desirable properties (low toxicity, high availability, low inflammability, high recyclability, low volatility and low price).

The aim of this work was to obtain coumarin derivatives, with potential lipoxygenase inhibiting activity, by environmentally friendly synthetic methods . Synthesis of coumarins were performed via Knoevenagel condensation between different substituted salicylaldehydes and active methylene compounds in deep eutectic solvents, which have role of the solvent and the catalyst. Synthesized coumarin derivatives showed enzyme inhibition in range from 45% to 96%.

Acknowledgement

This work has been supported in part by Croatian Science Foundation under the project “Green Technologies in Synthesis of Heterocyclic Compounds” (UIP-2017-05-6593).