Coumarin hybrids as privileged therapeutic scaffolds: biological activities, mechanistic insights, and therapeutic potential

Coumarin-based scaffolds have emerged as versatile structural platforms in modern medicinal chemistry due to their broad pharmacological spectrum and ease of functional modification. This review provides a comprehensive and up-to-date analysis of coumarin hybrid molecules reported between 2022 and 2026, highlighting recent advances in biological evaluation and its mechanistic understanding. Particular emphasis is placed on structurally diverse hybrids such as urea, hydroxamate, triazole-isatin, thiadiazole, and other multifunctional coumarin derivatives developed as therapeutic candidates across oncology, neurodegenerative disorders, and antimicrobial research. A systematic structure-activity relationship (SAR) discussion reveals that biological performance is strongly influenced by substitution patterns on the coumarin ring, linker length and flexibility, and the presence of pharmacophoric fragments enabling metal coordination, hydrogen bonding, and π-interactions. Hence, this review highlights the therapeutic significance of coumarin hybrids and their potential as promising lead scaffolds for future drug development.