Speeding up the Development of 5-[(4-Chlorophenoxy)-Methyl]-1,3,4-Oxadiazole-2-Thiol as Successful Oral Drug Candidate Based on Physicochemical Characteristics

Abstract

The present paper describes for the first time the oral-drug-qualifying predictors, anti-acetylcholinesterase activity, and molecular docking of a new compound, 5-[(4-chlorophenoxy)-methyl]-1,3,4-oxadiazole-2-thiol. The oral bioavailability predictors such as lipophilicity (logP), ionization constant (pKa), solubility (logS) and permeability (logD) were predicted using computational tools. Then, a UV spectrophotometric method was developed to verify the predicted properties and determine stability of the proposed compound in the presence of various stressors. The predicted logP and pKa values were very close to the measured values, while, the computed aqueous solubility (6.46 μg/mL) was lower than that found experimentally (65.00 μg/mL). The logS versus pH and logD versus pH plots indicated that the compound migrated to hydrophilic compartment on increasing pH. The compound remained stable under various photolytic and pH stress conditions. However, the compound exhibited degradation under oxidative and thermal stress. The results of the present study indicate that the proposed compound absorbs well from the oral route and remains stable at ambient temperature and physiological pH. The observed remarkable dose-dependent anti-acetylcholinesterase activity indicates that the compound may be a drug candidate for treating neurodegenerative disorders.