Synthesis, Pharmacological and Toxicological Screening of Penicillin-Triazole Conjugates (PNTCs).

A series of hybrid antimicrobial compounds were prepared by carboxylic acid protection of 6-aminopenicillanic acid using benzyl alcohol and thionyl chloride succeeded by azide displacement using trifluoromethanesulfonyl azide in dichloromethane. The azide thus formed was reacted with substituted alkynes to furnish benzyl-protected penicillin-triazole conjugates. Benzyl deprotection of the conjugates resulted in furnishing PNTCs under water methanol mixture using Pd/C as a catalyst. The PNTCs (-) formed were screened for antibacterial potency against pathogenic strains of , , , and and antifungal potency against , , and . Further antimicrobial evaluation revealed compounds , , , , and to be the most compounds of the series with minimum inhibitory concentration value for antibacterial in the range 0.5-50 μg/mL and for antifungal in the range 9-300 μg/mL. Toxicological analysis documented for compounds , , , , and revealed compound to be the most promising member of the series with 1000 and 500 mg/kg LD, and no-observed-adverse-effect level to facilitate future clinical studies of the same.