Polyoxins, antifungal antibiotics. XIII. Structure of polyoxins

Isono, Kiyoshi; Asahi, Ken-ichi; Suzuki, Saburô

doi:10.1021/ja01054a045

Cited by 339 publications

(108 citation statements)

References 8 publications

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“…Chitin is a major structural component of the cell walls of many fungi; inhibitors of chitin synthetase, such as the polyoxins (12,13) and nikkomycins (7,9), have been found to hinder fungal growth, although in some cases at much higher concentrations than those effective at the enzymatic level (2,10).…”

mentioning

confidence: 99%

Differential inhibition of chitin synthetases 1 and 2 from Saccharomyces cerevisiae by polyoxin D and nikkomycins

Cabib

1991

Antimicrob Agents Chemother

133

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Polyoxin D, nikkomycin X, and nikkomycin Z are all competitive inhibitors of chitin synthetase 2 (Chs2), the essential enzyme for primary septum formation in Saccharomyces cerevisiae, and of Chs1, a repair enzyme. However, Chs2 is more resistant to these antibiotics than Chs1. When Co2+, the best stimulator of Chs2, was used in the assay for this enzyme, the differences in the Ki values for nikkomycins between the two isozymes reached 3 orders of magnitude. These results point to differences in the active sites of the two isozymes. Polyoxin D was much more effective than nikkomycin Z in inhibiting cell growth. This underlines the importance of the choice of enzyme and of assay conditions when cell wall-synthesizing enzymes are used in screens for possible antifungal agents.

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confidence: 99%

Differential inhibition of chitin synthetases 1 and 2 from Saccharomyces cerevisiae by polyoxin D and nikkomycins

Cabib

1991

Antimicrob Agents Chemother

133

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“…The polyoxins, first described in 1965 (238), and the nikkomycins, described in 1976 (63), are peptide-nucleoside compounds produced by Streptomyces cacaoi and Streptomyces tendae, respectively. Both groups of compounds were isolated and described as a result of programs to discover fungicides and insecticides for agricultural use (63,124).…”

Section: Compounds Active Against Fungal Cell Walls Inhibitors Of Chimentioning

confidence: 99%

Compounds active against cell walls of medically important fungi

Hector

1993

Clin Microbiol Rev

215

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A number of substances that directly or indirectly affect the cell walls of fungi have been identified. Those that actively interfere with the synthesis or degradation of polysaccharide components share the property of being produced by soil microbes as secondary metabolites. Compounds specifically interfering with chitin or beta-glucan synthesis have proven effective in studies of preclinical models of mycoses, though they appear to have a restricted spectrum of coverage. Semisynthetic derivatives of some of the natural products have offered improvements in activity, toxicology, or pharmacokinetic behavior. Compounds which act on the cell wall indirectly or by a secondary mechanism of action, such as the azoles, act against diverse fungi but are usually fungistatic in nature. Overall, these compounds are attractive candidates for further development.

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“…asoensis which present a relevant antifungal activity by inhibition of chitin synthase. 1 The preparation of polyoxins is focused on the synthesis of the α-amino acid portion, (+)-polyoxamic acid, since the synthesis of its nucleoside residue is well described in literature. The purpose of this work is to propose a new approach to the synthesis of (+)-polyoxamic acid and derivatives starting from an asymmetric Morita-Baylis-Hillman (MBH) reaction.…”

Section: Introductionmentioning

confidence: 99%