From Structure to Function: Dibenzofuran Scaffold as a Versatile Platform for Diverse Biological Applications

Abstract:

The Dibenzofuran (DBF) scaffold represents a fundamental pharmacophore present in a wide spectrum of biologically active compounds. Its incorporation into molecular frameworks has been consistently associated with enhanced pharmacological potency, often surpassing that of structurally related analogs at equivalent concentrations. Numerous DBF-containing molecules have exhibited diverse therapeutic activities, including anti-microbial, anti-cancer, anti-amyloidogenic (particularly against transthyretin amyloidogenesis), anti-fungal, anti-inflammatory, anti-hyperglycemic, anti-hyperpigmentation, immunosuppressive, anti-HIV-1, anti-malarial, antipyretic, and analgesic effects. Understanding the chemical architecture of these compounds, particularly the influence of distinct functional groups on biological activity, offers valuable insights into their mechanisms of action. Moreover, Structure–Activity Relationship (SAR) analyses provide a rational basis for optimizing DBF derivatives and identifying molecular features responsible for their pharmacological diversity. This review categorizes and evaluates existing DBF derivatives, emphasizing their bioactivities, mechanisms of action, and therapeutic potential. The findings highlight the versatility of the DBF core as a multifunctional structural framework in modern drug design and discovery. Given its broad biological relevance, further exploration of DBF-based scaffolds through computational modeling, molecular docking, and synthetic modifications is recommended to identify novel analogs with improved selectivity, efficacy, and safety profiles. Such efforts could accelerate the development of next-generation therapeutics, establishing DBF as a cornerstone for innovative pharmaceutical research.