Hydantoin derivatives: A review on their anticancer activities

Abstract

Hydantoin, imidazolidine-2,4-dione, is an immensely valuable and highly favored heterocyclic scaffold in medicinal chemistry, as evidenced by its incorporation into several clinically approved drugs such as phenytoin, nitrofurantoin, and nilutamide. The hydantoin scaffold exhibits a wide range of pharmacological and biological properties, including antimicrobial, anticonvulsant, antidiabetic, anticancer, and anti-inflammatory activities. This comprehensive review primarily focuses on exploring the potential of hydantoin derivatives as anticancer agents, elucidating their various mechanisms of action such as histone deacetylase inhibition, modulation of B-cell lymphoma-2, interference with kinesin spindle proteins, inhibition of tubulin polymerization, and inhibition of epidermal growth factor receptor (EGFR). Moreover, this review underscores the importance of specific compounds and highlights the utility of pharmacophoric hybridization, wherein diverse bioactive groups are combined with hydantoin in a single molecule to achieve enhanced efficacy compared to individual scaffolds. Additionally, a concise analysis of the structure-activity relationships (SARs) is provided to offer insights into the correlation between the chemical structure of these compounds and their biological activity.