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Mar Drugs
2021 Feb 02;192:. doi: 10.3390/md19020081.
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Anti-Infective and Antiviral Activity of Valinomycin and Its Analogues from a Sea Cucumber-Associated Bacterium, Streptomyces sp. SV 21.
Wibowo JT
,
Kellermann MY
,
Köck M
,
Putra MY
,
Murniasih T
,
Mohr KI
,
Wink J
,
Praditya DF
,
Steinmann E
,
Schupp PJ
.
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The manuscript investigated the isolation, characterization and anti-infective potential of valinomycin (3), streptodepsipeptide P11A (2), streptodepsipeptide P11B (1), and one novel valinomycin analogue, streptodepsipeptide SV21 (4), which were all produced by the Gram-positive strain Streptomycescavourensis SV 21. Although the exact molecular weight and major molecular fragments were recently reported for compound 4, its structure elucidation was not based on compound isolation and spectroscopic techniques. We successfully isolated and elucidated the structure based on the MS2 fragmentation pathways as well as 1H and 13C NMR spectra and found that the previously reported structure of compound 4 differs from our analysis. Our findings showed the importance of isolation and structure elucidation of bacterial compounds in the era of fast omics technologies. The here performed anti-infective assays showed moderate to potent activity against fungi, multi drug resistant (MDR) bacteria and infectivity of the Hepatitis C Virus (HCV). While compounds 2, 3 and 4 revealed potent antiviral activity, the observed minor cytotoxicity needs further investigation. Furthermore, the here performed anti-infective assays disclosed that the symmetry of the valinomycin molecule is most important for its bioactivity, a fact that has not been reported so far.
Figure 1. Identified structures of the four valinomycin analogues 1–4. Based on our NMR and MS2 experiments, we assumed the absolute configuration to be identical to the one reported by Ye and colleagues [6].
Figure 2. Scheme of the fragmentation pathways of compounds 1–4. The m/z ratios were calculated and then compared with the MS2 fragment ions. The fragmentation started from the loss of a C=O unit.
Figure 3. The Hα/Cα region of the HSQC spectra of compounds 1–4 for D-Hiv/L-Lac on the left side and D-Val/L-Val on the right side. The spectra on the top represent the ones for streptodepsipeptide P11B (1) and the ones on the bottom for 4, respectively. The D-Hiv/L-Lac plots (left side) are divided into two subgroups: appr. 71 ppm (L-Lac) and appr. 79 ppm (D-Hiv). The same is true for the D-Val/L-Val plot (right side): appr. 59 ppm (D-Val) and appr. 60 ppm (L-Val).
Figure 4. Activity of compounds 1–4 to Huh7.5 cells that were infected with Hepatitis C Virus (HCV). (A) The percentage of HCV-infected hepatoma cells. (B) The viability of Huh7.5 cells after exposure to the test compounds. NC: negative control; and EGCG: epigallocatechin gallate as positive control.
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