Recent Developments in Ferulic Acid- and Caffeic Acid-Based Hybrids with Potential Anticancer Properties

Abstract

The shortage of effective chemotherapeutic agents poses a significant challenge to the global public health system. Cancer is among the leading diseases affecting the human population worldwide. Issues such as drug resistance, toxicity, lack of specificity, poor bioavailability and water solubility, and severe side effects reduce the effectiveness of many existing anticancer drugs. As a result, there is growing interest in discovering a new generation of therapeutic agents to overcome these limitations. Phenolic acids, including ferulic and caffeic acids, are cinnamic acid derivatives with numerous biological effects, including anti-inflammatory, antibacterial, antifungal, antioxidant, antiviral, cytotoxic, and antiproliferative effects. In recent years, drug repurposing and hybridization strategies have emerged as attractive approaches in medicinal chemistry because they may reduce both the cost and time associated with conventional drug discovery. As a result, several researchers have combined ferulic acid and caffeic acid scaffolds with different pharmacophores to generate hybrid compounds with enhanced anticancer potential. This review summarizes recent in vitro and in silico studies published between 2022 and 2025 on ferulic and caffeic acid hybrid compounds that exhibit cytotoxic and antiproliferative effects. Furthermore, the review discusses structure–activity relationship trends, synthetic approaches, and structural modifications associated with improved biological activity. Collectively, the findings highlight the significant potential of ferulic acid and caffeic acid scaffolds in the development of multifunctional anticancer agents.