Thiazolidine‐2,4‐dione and Thiazole Derivatives as Privileged Structures for Dengue Virus: A Review of Medicinal Chemistry Aspects

ABSTRACT Dengue fever is one of the greatest global health crises, with millions of infections annually and no effective antiviral therapy available. The high morbidity and mortality rate, combined with the rapid spread of the virus, highlights a critical failure in the fight against the disease. In this scenario, the search for new antiviral drugs is not only necessary, but urgent. Recently, thiazolidinedione (TZD) and thiazole derivatives have emerged as potential candidates for the treatment of dengue fever, challenging the paradigms of conventional therapies. These compounds represent a radically innovative approach by integrating direct antiviral activity—through selective inhibition of the NS2B‐NS3 protease and NS5 RNA polymerase—with the modulation of the inflammatory response, a key determinant in the progression of severe disease forms.The present study offers an in‐depth and innovative analysis of the therapeutic potential of these molecules, exploring in vitro and in silico assays and pharmacokinetic improvement strategies. The results reveal that TZDs and thiazoles have high affinity for strategic viral targets, effectively interrupting the DENV replication cycle and reducing the immunopathological effects of the infection. Unlike conventional antivirals, which fail to target a single mechanism of action, these molecules offer a multifunctional and disruptive approach, potentially redefining the treatment of dengue. By consolidating new therapeutic perspectives and providing a solid basis for future preclinical and clinical investigations, this study not only contributes to the advancement of biomedical science, but also represents a crucial milestone in the fight against one of the most neglected viruses in the world.