Synthetic Strategies and Structure Activity Relationships (SAR) of Biologically Active Coumarin-Based Hybrids

Coumarin (2-benzopyrone), a secondary plant metabolite, is considered a privileged scaffold in medicinal chemistry. Coumarin and its derivatives have been demonstrated to exhibit various biological activities such as antiviral, antibacterial, anticancer, anti-inflammatory, anticonvulsant, antioxidant, antidepressant, anti-Alzheimer, antidepressant, and antidiabetic. Because of its wide spectrum of biological activities, it has been explored extensively which has resulted in the development of many clinically useful drug molecules. Attempts have been made to prepare coumarin derivatives by either substituting them with a variety of aromatic heterocyclic rings and functionalities or by preparing its hybrids linked through an appropriate linker to obtain and develop potential therapeutic agents. The inclusion of natural secondary metabolites such as coumarin and its derivatives gained importance in the recent past to enhance biological activity. Coumarin moieties are easily synthesized by various chemical methods such as Knoevenagel reaction, Pechmann condensation, Kostanecki–Robinson coupling reaction, Claisen rearrangement, Michel addition reaction, Witting reaction, Reformatsky reaction, and Perkin reaction, and so on. The current review provides an overview of the classification of coumarins, and details of various approaches used for the synthesis of coumarin derivatives. Coumarin rings introduced in many synthetic compounds are discussed with structure-activity relationship (SAR) which are supported by their 2D molecular docking studies interaction within the receptors. The SAR of the coumarin derivatives will support the medicinal chemist in directing the synthesis of novel coumarin derivatives with diverse pharmacological properties.