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Molecules 2014, 19(10), 15653-15672; doi:10.3390/molecules191015653

Discovery of New Imidazole Derivatives Containing the 2,4-Dienone Motif with Broad-Spectrum Antifungal and Antibacterial Activity

1,†, 2,3,†, 1,* , 4, 2, 2,3, 1, 2,3,* and 1,*
1
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China
2
Radioimmunology and Clinical Laboratory, Luwan Branch, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200020, China
3
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
4
Humanwell Healthcare (Group) Co, Ltd., 666 Gaoxin Road, East Lake High-Tech Development Zone, Wuhan 430075, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 14 August 2014 / Revised: 14 September 2014 / Accepted: 18 September 2014 / Published: 29 September 2014
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [1827 KB, uploaded 29 September 2014]   |  

Abstract

A compound containing an imidazole moiety and a 2,4-dienone motif with significant activity toward several fungi was discovered in a screen for new antifungal compounds. Then, a total of 26 derivatives of this compound were designed, synthesized and evaluated through in vitro and in vivo antifungal activity assays. Several compounds exhibited improved antifungal activities compared to the lead compound. Of the derivatives, compounds 31 and 42 exhibited strong, broad-spectrum inhibitory effects toward Candida spp. In particular, the two derivatives exhibited potent antifungal activities toward the fluconazole-resistant isolate C. albicans 64110, with both having MIC values of 8 µg/mL. In addition, they had significant inhibitory effects toward two Gram-positive bacteria, Staphylococcus aureus UA1758 (compound 31: MIC = 8 µg/mL; compound 42: MIC = 4 µg/mL) and Staphylococcus epidermidis UF843 (compound 31: MIC = 8 µg/mL; compound 42: MIC = 8 µg/mL). The results of an animal experiment indicated that both compounds could improve the survival rate of model mice infected with ATCC 90028 (fluconazole-susceptible isolate). More importantly, the two compounds exhibited notable in vivo effects toward the fluconazole-resistant C. albicans isolate, which is promising with regard to the clinical problem posed by fluconazole-resistant Candida species. View Full-Text
Keywords: imidazole; 2,4-dienone; broad-spectrum; antifungal; antibacterial imidazole; 2,4-dienone; broad-spectrum; antifungal; antibacterial
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Liu, C.; Shi, C.; Mao, F.; Xu, Y.; Liu, J.; Wei, B.; Zhu, J.; Xiang, M.; Li, J. Discovery of New Imidazole Derivatives Containing the 2,4-Dienone Motif with Broad-Spectrum Antifungal and Antibacterial Activity. Molecules 2014, 19, 15653-15672.

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