6,7-Coumarin-heterocyclic hybrids: A comprehensive review of their natural sources, synthetic approaches, and bioactivity

The hybridization of heterocycles presents a key opportunity to craft innovative multicyclic compounds with enhanced biological activity. Coumarins, being broadly prevalent natural heterocycles, are extensively utilized in the formulation of diverse biologically and pharmacologically active chemicals. The fusion of various hetero rings with the coumarin ring represents a captivating approach to creating novel hybrid molecules endowed with notable biological activities. In the endeavor of developing heterocyclic-fused coumarins, a diverse array of 6,7heterocycle-coumarin hybrids has been introduced, showcasing remarkable biological efficacy. The impact of heterocyclic annulation at the 6,7-positions of the coumarin ring on the biological activity of the resultant structures has been examined. This review centers on the natural origins, synthetic methodologies, structural activity relationship investigation, and biological potentials of 6,7-heterocycle-coumarin hybrids. We conducted searches across several databases, including Web of Science, Google Scholar, PubMed, and Scopus. After sieving, we ultimately identified and included 161 pertinent studies published between 1995 and the middle of 2023. This will offer valuable insight to medicinal chemists for the future design and synthesis of biologically active lead compounds based on heterocycle-fused coumarin scaffolds with substantial therapeutic effects.