New Pyridobenothiazolone Derivatives Display Nanomolar Pan-Serotype Anti-Dengue Virus Activity.

ABSTRACT: Dengue virus (DENV) serotypes 1-4 are mosquito-borne flaviviruses that are responsible for significant morbidity and mortality worldwide, particularly in tropical and subtropical regions. Although two vaccines have been approved, their unbalanced efficacy across serotypes poses potential risks for specific populations. There are currently no approved antiviral treatments for DENV, resulting in a clear medical need, especially in endemic countries. Herein, a medicinal chemistry optimization of the pyridobenzothiazolone (PBTZ) derivative 2 is conducted, which results in the synthesis of a new series of PBTZ analogues. Compounds 15 and 19 exhibit nanomolar EC₅₀ values against all four DENV serotypes. While new PBTZ analogues do not inhibit DENV polymerase as the first series of PBT

SUBMITTER: Felicetti T 

PROVIDER: S-EPMC12221118 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature