Gossypol and Semisynthetic Derivatives: Chemistry, Bioactivities, and Mechanism of Actions

Gossypol, a polyphenolic compound predominantly derived from cotton plants, has garnered significant attention as a notable plant-derived bioactive compound with significant relevance in medicinal chemistry due to its diverse biological activities and potential therapeutic applications. Despite its inherent toxicity, gossypol exhibits insecticidal, antimicrobial, antiviral, antifertility, antiparasitic, anti-inflammatory, antioxidant, and anticancer properties. Furthermore, gossypol serves as a core molecule for synthesizing various derivatives, such as gossypol Schiff bases, gossypolone, and apogossypol, which are less toxic yet retain similar therapeutic benefits. The aim of this review is to provide a comprehensive overview of gossypol's diverse biological activities, with a particular focus on its anticancer potential, mechanisms of action, and recent advancements in its therapeutic applications. It highlights gossypol's wide-ranging biological activities, including its potent anticancer, antimicrobial, and antioxidant effects. Recent studies have shown promise in reducing gossypol's toxicity through the synthesis of derivatives, while advanced drug delivery methods, including nanocarriers, have been explored to enhance its therapeutic efficacy. Furthermore, gossypol has demonstrated significant synergistic potential when used in combination with conventional anticancer drugs, offering new avenues for cancer therapy.