Pyrazolo[3,4-<i>d</i>]pyrimidine-based neplanocin analogues identified as potential <i>de novo</i> pharmacophores for dual-target HBV inhibition.

ABSTRACT: The discovery of selective and potent inhibitors through de novo pathways is essential to combat drug resistance in chronic hepatitis B (CHB) infections. Recent studies have highlighted that neplanocin A (NepA) derivatives are biologically selective inhibitors of the hepatitis B virus (HBV). In this study, we designed, synthesized, and evaluated various pyrazolo[3,4-d]pyrimidine-based NepA analogues (4a-h) for their anti-HBV activity. Notably, analogue 4g demonstrated significant activity against HBV replication, with EC₅₀ (HBV DNA) = 0.96 μM, CC₅₀ > 100 μM and EC₅₀ (HBsAg) = 0.82 μM, showing selective inhibition of HBsAg secretion. The SAR analysis concluded that replacing the polar 4-NH₂ group with -CH₃ also acted as a

SUBMITTER: Kasula M 

PROVIDER: S-EPMC11840712 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature