DERIVATIVES OF 2-, 3-, 4-PYRIDINACETIC ACIDS AS POTENTIAL COMPONENTS OF FLUORINECONTAINING ANTICARIES AGENTS

Aim of the study. The present work performs a virtual screening of the biological activity and lipophilicity of several 2-, 3-, 4-pyridinacetic acids (PAA) derivatives. The selected compounds contain a pharmacophore of anti-inflammatory activity are commercially available and are of interest for the synthesis of potential anti-caries agents. The objects of the study are 14 PAA derivatives substituted with CH3, COOH, OCH3, F, Cl, Br, all of them included in the PubChem data base. Two typical anti-inflammatory drugs were chosen for comparison: diclofenac, a derivative of phenylacetic acid, and ibuprofen, a derivative of a phenylpropionic acid. The spectra of the potential biological activity of PAA derivatives were evaluated using the SwissTargetPrediction program. The LogP lipophilicity values of pyridines were calculated using the HyperChem program. The results of the calculations indicate a high probability of anti-inflammatory activity (Pa > 0,5) for 6 pyridines. The estimated Pa values exceed the corresponding values ones for unsubstituted PAA. Moreover, the presence of carboxyl and methoxy groups, fluorine, chlorine, and bromine atoms in the composition of PAA leads to a decrease in the Pa values of the anti-inflammatory activity (Pa ˂ 0,5), while the opposite is observed for the presence of a methyl group. The calculation data indicate an increased probability of analgesic and antiviral activity (against picornavirus, rhinovirus) for 2 and 7 of the studied pyridine derivatives, respectively. The estimated indicators of drug side effects – hepatotoxicity, nephrotoxicity, neurotoxicity, and hematotoxicity – show no increased likelihood for almost all of the studied pyridine derivatives, which is important in the context of their further possible use in the creation of new anticaries agents. 6-Methyl-2-pyridinoacetic acid, 2-methyl-4-pyridinoacetic acid, and 3-chloro-4-pyridinoacetic acid should be considered promising for the creation of new anti-caries agents based on pharmacological effects and physicochemical characteristics.