Functionalized Benzisoxazoles: Recent Developments in Diversified Synthetic Strategies and Cytotoxic Potential

Benzisoxazoles are pivotal heterocyclic scaffolds that have emerged as focal points in both synthetic and medicinal chemistry due to their broad synthetic applications and a wide spectrum of pharmacological properties. Their unique structural framework, along with the presence of an oxygen-nitrogen bond within a fused bicyclic ring system, confers remarkable physicochemical and biological properties, including anticancer, antibacterial, antifungal, antiviral, anti-inflammatory and diuretic activities. Appropriately constructed benzisoxazole scaffolds display remarkable potential to interact with a broad range of biological targets, thereby offering significant opportunities for the development of novel therapeutic agents with diverse mechanisms of action. Chemists have been intrigued by the fascinating properties of benzisoxazoles, and extensive scientific studies have been carried out to integrate the benzisoxazole scaffold into various bioactive compounds, including complex molecular frameworks. The past few years have witnessed tremendous progress in the development of various multicomponent one-pot synthetic strategies, including transition-metal catalysis, metal-free cyclization and microwave-assisted synthesis for diversely substituted benzisoxazole derivatives. This review highlights recent advancements in the synthetic chemistry of functionalized benzisoxazoles, including marketed drugs and agents in clinical trials. Furthermore, recent developments in the medicinal chemistry of benzisoxazole derivatives as anticancer agents, encompassing their mechanistic aspects, structure-activity relationships, and in silico studies, have been compiled. Drawing on the literature, the authors aim to provide a broad perspective and valuable insights for researchers, thereby inspiring and accelerating the development of novel benzisoxazole-appended anticancer therapeutics with significant biological implications.