Role of Heme in the Antifungal Activity of .......

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Role of Heme in the Antifungal Activity of the Azaoxoaporphine

Alkaloid Sampangine

(http://ec.asm.org/cgi/content/full/7/2/387)

The azaoxoaporphine alkaloid sampangine belongs to the aporphine

family of alkaloids, which have been reported to show antibacterial,

antifungal, antiviral, antiparasitic, and antitumor activities The

production of sampangine is associated with species within the plant

family Annonaceae (custard-apple family), including Duguetia

hadrantha and Cananga odorata Like other aporphine

alkaloids,sampangine is of particular interest as a potential

therapeutic agent, as it exhibits strong inhibitory activity against

the human fungal pathogens Candida albicans, Cryptococcus neoformans,

and Aspergillus fumigatus It also displays activity against the

bacterium Mycobacterium tuberculosis and the malaria parasite

Plasmodium falciparum and has activity against human cancer cells,

including malignant melanoma cells and HL-60 leukemia cells

Transcriptome response to sampangine in S. cerevisiae. Sampangine

displays potent antifungal activity, comparable to that of the widely

used drug amphotericin B, against the fungal pathogens C. albicans,

Candida glabrata, Candida kruseii, C. neoformans, and A. fumigatus

(Table 1). In order to understand the cellular effects of sampangine

in fungal cells, we made use of S. cerevisiae, an established model

organism that has been extensively used for elucidating the molecular

targets of antifungal and therapeutic compounds (reviewed in

references 56 and 64). A transcriptional profiling study was

conducted using S. cerevisiae cells that were treated with a

concentration of sampangine that resulted in 50% growth inhibition

(1.17 µg/ml). Genes that were significantly differentially expressed

between the treated and untreated cells (P value, 0.001) were

identified as described in Materials and Methods. A total of 204

genes showed expression changes in response to sampangine, with 129

genes showing increased expression and 75 genes showing decreased

expression. Data for a few selected genes are shown in Fig. 1 to

highlight the overall biological response to sampangine.

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Nice article Gail!