Discovery of in silico pharmacokinetic characteristics, drug-likeness, computational and experimental pKa values of selected unnatural fatty acid derivatives

The objective of this study was to synthesize a series of unnatural fatty acid derivatives, which have been identified as possessing distinctive properties and potential as new drug candidates. In light of the aforementioned considerations, it is imperative that the physicochemical profiles of these derivatives and their analogues be evaluated prior to the commencement of clinical trials, with a view to ascertaining their pharmacokinetic properties. In order to gain a deeper understanding of this phenomenon, a series of experimental and theoretical studies have been conducted. The pKa_exp values of these derivatives were determined for the first time by potentiometric titration. These derivatives, and in particular compounds C-E, display satisfactory physicochemical properties and medicinal chemistry. As a consequence of the related prediction studies, it was observed that the molecules A1-B violated the Lipinski rule by only one criterion, whereas the compounds C-E did not violate it at all. With the exception of compounds A1-A3, compounds B-E exhibit good oral bioavailability. All compounds demonstrated acceptable toxicity profiles, although further in vivo and in vitro laboratory studies are recommended to provide more detailed insights. Furthermore, all molecules were identified as bioactive protease and enzyme inhibitors.