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Article

Synthesis, Antifungal Activity, and Structure−Activity Relationships of Coruscanone A Analogues

Supporting Info

K. Suresh Babu,^† Xing-Cong Li,*^† Melissa R. Jacob,^† Qifeng Zhang,^† Shabana I. Khan,^† Daneel Ferreira,^†^‡ and Alice M. Clark^†^‡

National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences and Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, University, Mississippi 38677

J. Med. Chem., 2006, 49 (26), pp 7877–7886

DOI: 10.1021/jm061123i

Publication Date (Web): December 6, 2006

†

National Center for Natural Products Research.

To whom correspondence should be addressed. Phone: 662-915-6742. Fax: 662-915-7989. E-mail: xcli7@olemiss.edu.

‡

Department of Pharmacognosy.

Abstract

Coruscanone A, a plant-derived cyclopentenedione derivative, showed potent in vitro antifungal activity against Candida albicans and Cryptococcus neoformans comparable to amphotericin B and fluconazole. A series of analogues have been synthesized by modification of the cyclopentenedione ring, the enolic methoxy functionality, and the side chain styryl moiety of this natural product lead. A structurally close 1,4-benzoquinone analogue was also prepared. All the compounds were examined for their in vitro activity against major opportunistic fungal pathogens including C. albicans, C. neoformans, and Aspergillus fumigatus and fluconazole-resistant C. albicans strains, with several analogues demonstrating potent antifungal activity. Structure−activity relationship studies indicate that the 2-methoxymethylenecyclopent-4-ene-1,3-dione structural moiety is the pharmacophore responsible for the antifungal activity of this class of compounds while the side chain styryl-like moiety plays an important complementary role, presumably contributing to target binding.

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Published In Issue December 28, 2006
Received September 27, 2006

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Article

Synthesis, Antifungal Activity, and Structure−Activity Relationships of Coruscanone A Analogues