SYNTHESIS AND EVALUATION OF NOVEL α-CYANO-N-(4-HYDROXYPHENYL) CINNAMAMIDES FOR ANTIOXIDANT, ANTI-INFLAMMATORY ACTIVITIES: IN-SILICO PREDICTION OF DRUG LIKENESS PROPERTIES

A facile synthetic reaction has been used for the synthesis of novel compounds, substituted α-cyano-N-(4-hydroxyphenyl) cinnamamides from α-cyano-N-(4-hydroxyphenyl) acetamide. Their physical and spectral data characterized all the synthesized compounds. The title compounds were screened for in-vitro antioxidant activity in two different models which include scavenging of DPPH and nitric oxide free radicals. The compounds with hydroxy substitution on the phenyl ring of α-cyanocinnamamide moiety showed excellent antioxidant properties. Hence, the active compounds were evaluated for anti-inflammatory activity by carrageenan-induced rat paw edema assay. Among the evaluated compounds, α-cyano-N-(4-hydroxyphenyl)-4-hydroxy-3-methoxycinnamamide and α-cyano-N-(4-hydroxyphenyl)-3,4-dihydroxy-cinnamamide exhibited better activity comparable to the standard drug Diclofenac. Further, in-silico prediction of molecular properties of the synthesized compounds was carried out using molinspiration online software. The study revealed that all the compounds obeyed Lipinski’s rule of five. The TPSA calculations revealed that the compounds possess good intestinal absorption. Finally, the present study identified these compounds as potential new drug candidates for the treatment of diseases associated with oxidative stress.