9-O-butyl-13-(4-isopropylbenzyl)berberine, KR-72, is a potent antifungal agent that inhibits the growth of Cryptococcus neoformans by regulating gene expression

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Title
9-O-butyl-13-(4-isopropylbenzyl)berberine, KR-72, is a potent antifungal agent that inhibits the growth of Cryptococcus neoformans by regulating gene expression
Author(s)
S Bang; H Kwon; H S Hwang; K D Park; Sung Uk Kim; Y S Bahn
Bibliographic Citation
PLoS One, vol. 9, no. 10, pp. e109863-e109863
Publication Year
2014
Abstract
In this study we explored the mode or action of KR-72, a 9-O-butyl-13-(4-isopropylbenzyl)berberine derivative previously shown to exhibit potent antifungal activity against a variety of human fungal pathogens. The DNA microarray data revealed that KR-fl treatment significantly changed the transcription profiles of C. neoformans, affecting the expression of more than 2,000 genes. Genes involved in translation and transcription were mostly upregulated, whereas those involved in the cytoskeleton, intracellular trafficking, and lipid metabolism were downregulated. KR-fl also exhibited a strong synergistic effect with the antifungal agent FK506. KR-72 treatment regulated the expression of several essential genes, including ECM16, NOP14, HSP10 and MGE1, which are required for C. neoformans growth. The KR-72-mediated induction of MGEI also likely reduced the viability of C. neoformons by impairing cell cycle or the DNA repair system. In conclusion, KR-fl showed antifungal activity by modulating diverse biological processes through a mode of action distinct from those of clinically available antifungal drugs such as polyene and azole drugs.
ISSN
1932-6203
Publisher
Public Library of Science
DOI
http://dx.doi.org/10.1371/journal.pone.0109863
Type
Article
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