Quinoxaline Derivatives (2020-2025): Emerging Therapeutic Applications and Opportunities for Drug Repurposing.

Quinoxaline derivatives, formed by the fusion of two aromatic rings, benzene and pyrazine, possess a broad spectrum of pharmacological activities including antimicrobial, anticancer, anti-inflammatory, neuroprotective, antiparasitic and antidiabetic effects, which have attracted considerable attention in the field of medicinal chemistry. This review aims to present recent advances (2020-2025) in the pharmacological potential of the quinoxaline scaffold and to highlight its emerging role in drug-repurposing strategies. A comprehensive literature review was conducted across major databases to identify publications describing the chemical synthesis, biological evaluation, mechanisms of action, and pharmacokinetic properties of quinoxaline derivatives. The collected data were analyzed to identify the key Structure- Activity Relationships (SARs), therapeutic trends, and existing translational challenges. Despite their promising biological properties, quinoxaline derivatives possess important limitations, such as poor aqueous solubility, variable bioavailability, and potential toxicity. These challenges have been partially addressed, and their therapeutic potential has been expanded by recent advances in structural optimization, nanocarrier-based delivery systems, and computational drug design. Compared with other heterocyclic scaffolds, such as indole, pyrazole, benzothiazole, and quinoline, quinoxalines provide an advantageous balance between structural versatility, pharmacological diversity, and modifiability. These characteristics make them attractive scaffolds for drug repurposing.