Journal of Antimicrobial Chemotherapy (1999) 43, 667-674
© 1999 The British Society for Antimicrobial Chemotherapy
Differential inhibitory effects of protoberberines on sterol and chitin biosyntheses in Candida albicans
a Department of Biochemistry and Bioproducts Research Center, Yonsei University, 134 Shinchon-dong, Sudemoon-ku, Seoul 120-749, South Korea; b Department of Microbiology, University of Leeds, Leeds LS2 9JT, UK; c Han Wha Group Research and Engineering Center, Taejeon 305-345, South Korea
The anti-Candida potentials of 12 Korean medicinal plants were explored: methanol extracts from Coptis rhizoma and Phellodendron amurense caused significant inhibition of growth of Candida albicans, Candida glabrata, Candida krusei and Candida parapsilosis. The predominant active components of the extracts were the protoberberines berberine and palmatine; the most potent inhibition of growth was exhibited by berberine on C. krusei (MIC <4 mg/L) and palmatine on C. parapsilosis (MIC 16 mg/L). Both berberine and palmatine inhibited the in-vivo rate of incorporation of L-[methyl- 14C]methionine into C-24 of ergosterol in C. albicans (50% inhibition concentration (IC 50 values), 25 µM and 300 µM, respectively); this result suggests that sterol 24-methyl transferase (24-SMT) is one of the cellular targets for the antifungal activity of the protoberberines. In-vitro 24-SMT activity in microsomes from the yeast growth form of C. albicans was inhibited by both berberine (inhibition constant (K i) 232 µM) and palmatine (K i 257 µM) in a non-competitive manner; inhibition of 24-SMT was more marked for the mycelial form than for the yeast growth form of this organism. Palmatine inhibited chitin synthase from both the yeast and mycelial growth phases of C. albicans in a non-competitive manner (K i 780 µM). The effects of protoberberines, extracted from established medicinal plants, on both sterol and cell wall biosyntheses in pathogenic fungi, indicate that the potential of these compounds, or their semi-synthetic derivatives, as a novel class of antifungal agents should be investigated more fully.
* Corresponding address. Department of Biochemistry, Room 513, Science Building, College of Science, Yonsei University, 134 Shinchon-dong, Seoul, 120-749, south Korea. Tel: +82-2-361-2702; Fax: +82-2-362-9897; E-mail: paikyk{at}bubble.yonsei.ac.kr
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