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. 2014 Jan 21;12(1):491-507.
doi: 10.3390/md12010491.

Hyaluromycin, a new hyaluronidase inhibitor of polyketide origin from marine Streptomyces sp

Enjuro Harunari  1 , Chiaki Imada  2 , Yasuhiro Igarashi  3 , Takao Fukuda  4 , Takeshi Terahara  5 , Takeshi Kobayashi  6
Affiliations

Hyaluromycin, a new hyaluronidase inhibitor of polyketide origin from marine Streptomyces sp

Enjuro Harunari et al. Mar Drugs. .

Abstract

Hyaluromycin (1), a new member of the rubromycin family of antibiotics, was isolated from the culture extract of a marine-derived Streptomyces sp. as a HAase inhibitor on the basis of HAase activity screening. The structure of 1 was elucidated through the interpretation of NMR data for the compound and its 3″-O-methyl derivative in combination with an incorporation experiment with [1,2-13C2]acetate. The compound's absolute configuration was determined by the comparison of its circular dichroism (CD) spectrum with those of other rubromycins. Hyaluromycin (1) consists of a γ-rubromycin core structure possessing a 2-amino-3-hydroxycyclopent-2-enone (C5N) unit as an amide substituent of the carboxyl function; both structural units have been reported only from actinomycetes. Hyaluromycin (1) displayed approximately 25-fold more potent hyaluronidase inhibitory activity against hyaluronidase than did glycyrrhizin, a known inhibitor of plant origin.

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Figures

Figure 1
Figure 1
Natural rubromycins.
Figure 2
Figure 2
Natural products containing the C5N substructure.
Figure 3
Figure 3
Families of compounds containing the C5N substructure.
Figure 4
Figure 4
Structure of hyaluromycin (1).
Figure 5
Figure 5
1H-1H COSY and HMBC correlations of compound 1.
Figure 6
Figure 6
HPLC chromatogram of methylated derivatives of 1.
Figure 7
Figure 7
13C NMR spectrum of [1,2-13C2]acetate-labeled 2.
Figure 8
Figure 8
1H-1H COSY and HMBC correlations of [1,2-13C2]acetate-labeled 2.
Figure 9
Figure 9
13C-13C couplings observed in 2D INADEQUATE (a,b) and 13C (c) NMR spectra of [1,2-13C2]acetate-labeled 2. The coupling of C-1″/C-5″ and C-3″/C-4″ were only observed in the 13C NMR spectrum (c). (a) Optimized for 1Jcc = 50 Hz; (b) Optimized for 1Jcc = 35 Hz; (c) 13C NMR spectra; (d) Observed in 2D INADEQUATE.
Figure 10
Figure 10
CD spectrum and absolute configuration of 2.
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References

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