Synthesis, Characterization, and Preliminary Evaluation of Antimicrobial activity of Imines derived from Vanillic Acid Conjugated to Heterocyclic 4H- 1,2,4-Triazole-3-Thiol

Abstract

Triazole is a significant heterocyclic moiety that occupies a distinctive area in heterocyclic chemistry because of its numerous biological actions. In terms of clinically useful drug options, 1,2,4-triazole has a wide range of activities, including analgesic, antiseptic, antimicrobial, antioxidant, anti-inflammatory, diuretic, anticancer, anticonvulsant, and antidiabetic agents. Vanillic acid is a phenolic substance that can be found in many foods and medicinal plants; it has antioxidant, antimicrobial, anti-inflammatory, anti-cancer, and anti-obesity properties. The purpose of this research is to prepare new imines derived from vanillic acid conjugated to heterocyclic 4H- 1,2,4-triazole-3-thiol (5-8) and evaluate their antimicrobial activity. A multistep synthesis was established for the preparation of new vanillic acid-triazole conjugates, this is done by synthesis of the intermediate 4-(4-amino-5-sulfanyl-4H-1,2,4-triazol-3-yl)-2-methoxyphenol (compound 4), which then reacts with different heterocyclic aldehydes to give the corresponding 4-(4- (substituted amino)-5-mercapto-4H-1,2,4triazol-3-yl)-2- methoxy phenol derivatives (5-8). These compounds were characterized spectroscopically by FT- IR and 1H- NMR. These imine derivatives (5-8) were tested for their antimicrobial activity and compared with three standard references (amoxicillin, ciprofloxacin, and fluconazole). Overall, compounds 6 and 8 exhibited varying degrees of inhibitory effects on the growth of the examined bacterial species and fungus. The most active one is compound 6 having pyrrole ring imine derivative showed potent activity against C. albicans and moderate activity against all tested bacteria compared to other derivatives but no activity toward P. aeruginosa and P. mirabilis. Moreover, only compounds 5 and 7 having thiophene group showed moderate inhibitory activity toward P. aeruginosa, while compounds 6 and 8 had no effect.