Enantiomer-Resolved Biological Profiling and Chiral Developability Assessment of Novel Naphthylethyl Thioureas.

Background/

Objectives

Stereochemistry can substantially influence the biological activity and pharmaceutical properties of small molecules. This study investigated the stereochemistry-dependent biological activity and chiral recognition of novel naphthylethyl thiourea enantiomers using an integrated biological, chromatographic, and computational approach.

Methods

Ten pairs of naphthylethyl thiourea enantiomers were synthesized from enantiomerically pure precursors and characterized. Antiproliferative and antibacterial activity, chiral HPLC behavior on polysaccharide- and protein-based stationary phases, molecular docking, and multivariate relationships were evaluated.

Results

Target-dependent enantioselectivity and substituent-dependent activity patterns were observed. All enantiomeric pairs were chromatographically distinguished under at least one condition, and selected compounds showed selector- and mobile-phase-dependent changes in elution order. AGP-based chromatography showed stereoselective recognition for a subset of compounds, while computational analyses provided complementary support for the experimental trends.

Conclusions

Stereochemistry and substitution jointly influence biological and chromatographic behavior in this thiourea series. Integrated biological, chromatographic, and computational profiling provides a useful framework for early enantiomer-resolved developability assessment.