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Molecules 2012, 17(12), 14022-14036; doi:10.3390/molecules171214022
Article

Antifungal Activity of Homoaconitate and Homoisocitrate Analogs

1,* , 1, 2, 2 and 2
Received: 15 October 2012; in revised form: 14 November 2012 / Accepted: 15 November 2012 / Published: 27 November 2012
(This article belongs to the Special Issue Advances in Medicinal Chemistry of Antifungals)
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Abstract: Thirteen structural analogs of two initial intermediates of the L-a-aminoadipate pathway of L-lysine biosynthesis in fungi have been designed and synthesized, including fluoro- and epoxy-derivatives of homoaconitate and homoisocitrate. Some of the obtained compounds exhibited at milimolar range moderate enzyme inhibitory properties against homoaconitase and/or homoisocitrate dehydrogenase of Candida albicans. The structural basis for homoisocitrate dehydrogenase inhibition was revealed by molecular modeling of the enzyme-inhibitor complex. On the other hand, the trimethyl ester forms of some of the novel compounds exhibited antifungal effects. The highest antifungal activity was found for trimethyl trans-homoaconitate, which inhibited growth of some human pathogenic yeasts with minimal inhibitory concentration (MIC) values of 16–32 mg/mL.
Keywords: homoisocitrate; homoaconitate; synthesis; inhibitors; molecular modeling; antifungal activity homoisocitrate; homoaconitate; synthesis; inhibitors; molecular modeling; antifungal activity
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.

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MDPI and ACS Style

Milewska, M.J.; Prokop, M.; Gabriel, I.; Wojciechowski, M.; Milewski, S. Antifungal Activity of Homoaconitate and Homoisocitrate Analogs. Molecules 2012, 17, 14022-14036.

AMA Style

Milewska MJ, Prokop M, Gabriel I, Wojciechowski M, Milewski S. Antifungal Activity of Homoaconitate and Homoisocitrate Analogs. Molecules. 2012; 17(12):14022-14036.

Chicago/Turabian Style

Milewska, Maria J.; Prokop, Marta; Gabriel, Iwona; Wojciechowski, Marek; Milewski, Sławomir. 2012. "Antifungal Activity of Homoaconitate and Homoisocitrate Analogs." Molecules 17, no. 12: 14022-14036.


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