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. 2019 Jun 15;24(12):2239.
doi: 10.3390/molecules24122239.

Osmanicin, a Polyketide Alkaloid Isolated from Streptomyces osmaniensis CA-244599 Inhibits Elastase in Human Fibroblasts

Mamdouh N Samy  1 , Géraldine Le Goff  2 , Philippe Lopes  3 , Katerina Georgousaki  4 , Sentiljana Gumeni  5 , Celso Almeida  6 , Ignacio González  7 , Olga Genilloud  8 , Ioannis Trougakos  9 , Nikolas Fokialakis  10 , Jamal Ouazzani  11
Affiliations

Osmanicin, a Polyketide Alkaloid Isolated from Streptomyces osmaniensis CA-244599 Inhibits Elastase in Human Fibroblasts

Mamdouh N Samy et al. Molecules. .

Abstract

The strain Streptomyces osmaniensis CA-244599 isolated from the Comoros islands was submitted to liquid-state fermentation coupled to in situ solid-phase extraction with amberlite XAD-16 resin. Elution of the trapped compounds on the resin beads by ethyl acetate afforded seven metabolites, osmanicin (1), streptazolin (2), streptazone C (3), streptazone B1 (4), streptenol C (5), nocardamine (6) and desmethylenylnocardamine (7). Osmanicin (1) is a newly reported unusual scaffold combining streptazolin (2) and streptazone C (3) through a Diels-Alder type reaction. Experimental evidence excluded the spontaneous formation of 1 from 2 and 3. The isolated compounds were evaluated for their ability to inhibit elastase using normal human diploid fibroblasts. Compound 1 exhibited the most potent activity with an IC50 of 3.7 μM.

Keywords: Streptomyces osmaniensis; alkaloids; elastase inhibition; in situ solid-phase extraction; osmanicin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Phylogenetic analysis of Actinomycete isolate CA-244599.
Figure 2
Figure 2
Relative (%) elastase inhibitory activity in normal human BJ fibroblasts after 24 h of treatment with shown extracts at the concentration of 1 and 10 µg/mL. Values from controls (cells treated without the extract) were set to 100%. Data are presented as mean ± SD (n ≥ 3). The statistical differences observed in the graphic are significant when compared to control samples, * p < 0.05.
Figure 3
Figure 3
Compounds isolated from Streptomyces osmaniensis CA-244599.
Figure 4
Figure 4
Key COSY and HMBC correlations for compound 1.
Figure 5
Figure 5
Confirmation of the stereochemistry at C-6.
Figure 6
Figure 6
The proposed biosynthetic pathway of osmanicin (1).
Figure 7
Figure 7
Relative (%) elastase inhibitory activity in human fibroblasts after 24 h of treatment with pure compounds at the concentration 5 μM. Values from controls (cells treated without the extract) were set to 100%. Data are presented as mean ± SD (n = 3). Shown differences are significant vs. control samples, * p < 0.05.
Figure 8
Figure 8
Determination of the IC50 inhibitory concentration of osmanicin against elastase (A) and cell survival after osmanicin treatment (B). (A) The half maximal inhibitory concentration (IC50) of osmanicin against elastase was calculated by plotting the graph between the different concentrations used (1 μM to 5 μM) and the % inhibition of elastase activity. Data are presented as mean ± SD (n ≥ 3). (B) Relative (%) survival (MTT assay) of BJ fibroblasts exposed to the indicated concentrations of osmanicin for 24 h. Data are presented as mean ± SD (n ≥ 3).
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