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Vol. 26 No. 10 (2014): Vol 26 Issue 10

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Synthesis, Antibacterial Evaluation and Molecular Docking Study of Nitazoxanide Analogues

https://doi.org/10.14233/ajchem.2014.16038
X.W. Liu
Key Laboratory of New Animal Drug Project, Gansu Province; Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture; Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, P. R. China
H. Zhang
Key Laboratory of New Animal Drug Project, Gansu Province; Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture; Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, P. R. China
Y.J. Yang
Key Laboratory of New Animal Drug Project, Gansu Province; Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture; Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, P. R. China
J.Y. Li
Key Laboratory of New Animal Drug Project, Gansu Province; Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture; Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, P. R. China
B. Li
Key Laboratory of New Animal Drug Project, Gansu Province; Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture; Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, P. R. China
X.Z. Zhou
Key Laboratory of New Animal Drug Project, Gansu Province; Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture; Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, P. R. China
J.Y. Zhang
Key Laboratory of New Animal Drug Project, Gansu Province; Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture; Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, P. R. China

Corresponding Author(s) : J.Y. Li

lijy1971@163.com; xiwangliu@126.com

Asian Journal of Chemistry, Vol. 26 No. 10 (2014): Vol 26 Issue 10

Abstract

A series of nitazoxanide analogues were synthesized and characterized by means of 1H NMR, 13C 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.

Keywords

Nitazoxanide analogues Synthesis Antibacterial activity Molecular docking
Liu, X., Zhang, H., Yang, Y., Li, J., Li, B., Zhou, X., & Zhang, J. (2014). Synthesis, Antibacterial Evaluation and Molecular Docking Study of Nitazoxanide Analogues. Asian Journal of Chemistry, 26(10), 2921–2926. https://doi.org/10.14233/ajchem.2014.16038
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