Synthesis, Antibacterial Evaluation and Molecular Docking Study of Nitazoxanide Analogues

A series of nitazoxanide analogues were synthesized and characterized by means of H-1 NMR, C-13 NMR and HR-MS. The antibacterial activities of synthesized compounds against Clostridium difficile were evaluated and 1d was the most promising compound. The preliminary results showed that compounds containing nitro-substituted thiazole ring displayed notable activities. Compounds that thiazole moiety replaced by a pyrimidine ring exhibited moderate activities. Molecular docking study of nitazoxanide and 1d with pyruvate ferredoxin oxidoreductase suggested that the nitro group interacts with thiamine pyrophosphate and surrounding amino acids, which were almost same compared with pyruvate. The results revealed that nitazoxanide may be a competitive inhibitor of pyruvate and nitro-group is necessary for thiazolide's activities against anaerobic organisms containing pyruvate ferredoxin oxidoreductase enzyme.