A comparison of the chitin synthase-inhibitory and antifungal efficacy of nucleoside-peptide antibiotics: structure-activity relationships |
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Authors: | Rolf Furter Dora M. Rast |
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Affiliation: | University of Zürich, Institute of Plant Biology, Zollikerstrasse 107, CH-8008 Zürich, Switzerland |
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Abstract: | Abstract Using Mucor rouxii , the chitin synthase (ChS)-inhibitory and antifungal activity was determined of 6 nucleoside-peptide antibiotics (NPAs) representing pairs of structural analogues, each consisting of a dipeptide (DP) and a corresponding tripeptide (TP). These were the nikkomycins X and I (X, I), the nikkomycins Z and J (Z, J), and the polyoxins D and A (D, A). Although all were very good ChS-inhibitors (X and A being best, with K i approx. 0.5 μM), only X and Z elicited a strong response in vivo as determined by the degree of inhibition exerted on N -acetylglucosamine (GlcNAc) incorporation into the chitin fraction, the survival rate, and the minimum inhibitory concentration (MIC). The MIC values were about 2 μM (for X and Z) and 100 μM (for I, J, D and A). Certain DPs and TPs reduced the antifungal activity of X, the effect being much more pronounced with DPs. It is suggested that uptake of NPAs involves the transpeptidase reaction of the γ-glutamyl cycle, the observed antagonism thus resulting from competition for a common carrier. |
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Keywords: | Nikkomycins polyoxins Ki values MIC values type of fungitoxicity antagonism of antifungal action by di- and tripeptides Mucor rouxii |
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