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J Nat Prod. 2012 Apr 27;75(4):707-15. doi: 10.1021/np2009994. Epub 2012 Mar 8.

Waikialoid A suppresses hyphal morphogenesis and inhibits biofilm development in pathogenic Candida albicans.

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1
Natural Products Discovery Group, Stephenson Life Sciences Research Center, 101 Stephenson Parkway, Room 1000, University of Oklahoma, Norman, Oklahoma 73019-5251, USA.

Abstract

A chemically prolific strain of Aspergillus was isolated from a soil sample collected near Waikiki Beach, Honolulu, Hawaii. The fungus produced several secondary metabolites, which were purified and placed in our natural products library and were later screened for substances capable of inhibiting biofilm formation by Candida albicans. It was determined that one of the secondary metabolites from the Hawaiian fungal isolate, a new complex prenylated indole alkaloid named waikialoid A (1), inhibited biofilm formation with an IC(50) value of 1.4 μM. Another structurally unrelated, presumably polyketide metabolite, waikialide A (15), also inhibited C. albicans biofilm formation, but was much less potent (IC(50) value of 32.4 μM). Microscopy studies revealed that compound 1 also inhibited C. albicans hyphal morphogenesis. While metabolite 1 appears ineffective at disrupting preformed biofilms, the accumulated data indicate that the new compound may exert its activity against C. albicans during the early stages of surface colonization involving cell adherence, hyphal development, and/or biofilm assembly. Unlike some other stephacidin/notoamide compounds, metabolite 1 was not cytotoxic to fungi or human cells (up to 200 μM), which makes this an intriguing model compound for studying the adjunctive use of biofilm inhibitors in combination with standard antifungal antibiotics.

PMID:
22400916
PMCID:
PMC3338887
DOI:
10.1021/np2009994
[Indexed for MEDLINE]
Free PMC Article
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