Synthesis, biological evaluation and molecular docking analysis of p-tolyldiazenyl azo derivatives

Impacts of multiresistant bacteria such as Staphylococcus aureus and Escherichia coli have initiated active research of new effective drugs. Herein, new p-tolyldiazenyl azo derivatives 1-13 were successfully synthesized through a well-established diazo coupling reaction of p-toluidine with substituted phenol at ortho, meta and para positions. The series was obtained in a moderate yield of 58% – 79% and structural elucidation was done using FTIR and NMR spectroscopies. The antioxidant ability of the compounds 1-13 evaluated by 2,2’-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assay outlined a potential activity with IC50 of 26 – 188 ppm and 12.29 – 182.73 mg/mL Trolox equivalent, respectively. Moreover, the antibacterial activity of the compounds assessed via the Kirby-Bauer disc diffusion method against S.aureus and E.coli show moderate to good inhibition zone of 7.04±0.50 mm to 17.46±0.50 mm as compared to standard ampicillin (19.29±0.33 mm). Determination of minimum inhibitory concentration (MIC) through a turbidimetric method towards similar bacteria strains, gave a MIC values of 84 – 178 ppm (S.aureus) and 112 – 194 ppm (E.coli) with compound 3 (m-F) (84.37 ppm) and 9 (mBr) (112.40 ppm) are better than ampicillin which the MIC were 97.70 ppm and 112.92 ppm for S.aureus and E.coli respectively. The molecular docking analysis towards MurE and DHFR enzymes reveals that the hydrogen bonding, hydrophobic and electrostatic interactions with amino acid in the vicinity are the major contributions to the activities. This study is important in discovering a potentially new candidate for combating emerging infections.