In vitro evaluation of tropolone absorption, metabolism, and clearance.

ABSTRACT: Tropolone compounds can inhibit hepatitis B virus (HBV) replication at sub-micromolar levels and are synergistic upon co-treatment with nucleos(t)ide analog drugs. However, only a few compounds within this chemotype have been screened for their pharmacological properties. Here, we chose 36 structurally diverse tropolones from six subclasses to characterize their in vitro pharmacological parameters. All compounds were more soluble in pHs that reflect the gastrointestinal tract (pH 5 and 6.5) than plasma (pH 7.4). Those compounds that had solubility limits >100 μM were tested in a passive permeability assay, and there was no general trend in the compounds' passive permeability at any pH. Twenty-nine compounds with the best absorption parameters were tested in HEK293 cells to assess potential

SUBMITTER: Woodson ME 

PROVIDER: S-EPMC10843707 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature