Evaluating the ADMET properties of Isosteric Substiution in Schiff Base Derivatives

Abstract

Three Schiff base analogues (1–3) derived from Nilofabicin by incorporating ortho-substituted aldehydes (OH, NH₂, SH) were evaluated via in silico ADMET profiling. Compound 1 with OH substituent demonstrated the most favorable pharmacokinetic properties, including high gastrointestinal absorption, acceptable lipophilicity, and compliance with multiple drug-likeness rules. While compound 2 with NH₂ group also showed promising characteristics, compound 3 (SH substituent) exhibited drawbacks such as low solubility and absorption. These results highlight the impact of isosteric substitutions on drug-likeness and oral bioavailability.