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A New Analogue of Echinomycin and a New Cyclic Dipeptide from a Marine-Derived Streptomyces sp. LS298.

Zhen X, Gong T, Liu F, Zhang PC, Zhou WQ, Li Y, Zhu P - Mar Drugs (2015)

Bottom Line: Furthermore, the differences in NMR data of keto-enol tautomers in tirandamycins were discussed for the first time.Compound 1 exhibited moderate antibacterial activities against Staphylococcuse pidermidis, S. aureus, Enterococcus faecium, and E. faecalis with the minimum inhibitory concentration (MIC) values ranged from 16 to 64 μg/mL.Moreover, it displayed remarkable anti-tumor activities; the highest activity was observed against the Jurkat cell line (human T-cell leukemia) with an IC50 value of 0.414 μM.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Xicheng District, Beijing 100050, China. zhenxin@imm.ac.cn.

ABSTRACT
Quinomycin G (1), a new analogue of echinomycin, together with a new cyclic dipeptide, cyclo-(l-Pro-4-OH-l-Leu) (2), as well as three known antibiotic compounds tirandamycin A (3), tirandamycin B (4) and staurosporine (5), were isolated from Streptomyces sp. LS298 obtained from a marine sponge Gelliodes carnosa. The planar and absolute configurations of compounds 1 and 2 were established by MS, NMR spectral data analysis and Marfey's method. Furthermore, the differences in NMR data of keto-enol tautomers in tirandamycins were discussed for the first time. Antibacterial and anti-tumor activities of compound 1 were measured against 15 drug-sensitive/resistant strains and 12 tumor cell lines. Compound 1 exhibited moderate antibacterial activities against Staphylococcuse pidermidis, S. aureus, Enterococcus faecium, and E. faecalis with the minimum inhibitory concentration (MIC) values ranged from 16 to 64 μg/mL. Moreover, it displayed remarkable anti-tumor activities; the highest activity was observed against the Jurkat cell line (human T-cell leukemia) with an IC50 value of 0.414 μM.

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The Key HMBC and NOE correlations of compound 2.
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marinedrugs-13-06947-f003: The Key HMBC and NOE correlations of compound 2.

Mentions: Cyclo(l-Pro-4-OH-l-Leu) (2) was isolated as a white powder, its molecular formula C11H18N2O3 was established upon the analysis of the HRESIMS peak at m/z 249.1209 [M + Na]+, indicating four degrees of unsaturation. The 1H NMR spectrum of 2 (Table 3) revealed one NH resonance (δH: 7.66 (1H, s)); two methine signals (δH: 4.23 (1H, d, J = 10.5 Hz), 4.08 (1H, t, J = 8.0 Hz)); four methylene resonances (δH: 3.56 (2H, m); 2.01 (1H, m), 1.89 (1H, m); 2.36 (1H, dd, J = 8.5, 2.5 Hz), 2.10 (1H, m); 2.32 (1H, dd, J = 14.5, 2.0 Hz), 1.79 (1H, dd, J = 14.5, 11.0 Hz)); two methyl signals in the upfield region (δH: 1.31 (1H, s), 1.35 (1H, s)). The 13C NMR spectra of 2 (Table 3) showed a total of 11 carbon resonances, and they were classified as two amide carbonyls (δC: 169.7, 166.1), three methines (δC: 70.9, 58.8, 53.2), four methylene signals (δC: 45.6, 41.1, 28.3, 22.6), two methyl signals (δC: 32.3, 27.4). Further analysis of the NMR data confirmed the existence of moieties of Pro and 4-hydroxyl-Leu. In the HMBC experiment (Figure 3), the correlations of H-3 (δH: 3.56 (2H, m)), and H-9 (δH: 4.23 (1H, d, J = 10.5 Hz)) with C-1 (δC: 166.1); H-5 (δH: 2.36 (1H, dd, J = 8.5, 2.5 Hz), 2.10 (1H, m)) and H-8 (δH: 7.66 (1H, s)) with C-6 (δC: 58.8) confirmed the planar structure for compound 2 was cyclo(Pro-4-hydroxyl-Leu). The relative stereochemistry of 2 was deduced from the NOE spectrum (Figure 3). When irradiating H-6 at δH: 4.08 and H-9 at δH: 4.23, the integration values of H-9 and H-6 were enhanced respectively, which showed that H-6 and H-9 positioned cis to each other. That is to say relative configurations of Pro and 4-hydroxyl-Leu were either l or d configurations. On the basis of Marfey’s method, the presence of l-Pro in 2 compared with the appropriate amino acid standards (Table 2, Supplementary Materials Figure S17), determined the configuration of compound 2 as cyclo(l-Pro-4-hydroxyl-l-Leu).


A New Analogue of Echinomycin and a New Cyclic Dipeptide from a Marine-Derived Streptomyces sp. LS298.

Zhen X, Gong T, Liu F, Zhang PC, Zhou WQ, Li Y, Zhu P - Mar Drugs (2015)

The Key HMBC and NOE correlations of compound 2.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663560&req=5

marinedrugs-13-06947-f003: The Key HMBC and NOE correlations of compound 2.
Mentions: Cyclo(l-Pro-4-OH-l-Leu) (2) was isolated as a white powder, its molecular formula C11H18N2O3 was established upon the analysis of the HRESIMS peak at m/z 249.1209 [M + Na]+, indicating four degrees of unsaturation. The 1H NMR spectrum of 2 (Table 3) revealed one NH resonance (δH: 7.66 (1H, s)); two methine signals (δH: 4.23 (1H, d, J = 10.5 Hz), 4.08 (1H, t, J = 8.0 Hz)); four methylene resonances (δH: 3.56 (2H, m); 2.01 (1H, m), 1.89 (1H, m); 2.36 (1H, dd, J = 8.5, 2.5 Hz), 2.10 (1H, m); 2.32 (1H, dd, J = 14.5, 2.0 Hz), 1.79 (1H, dd, J = 14.5, 11.0 Hz)); two methyl signals in the upfield region (δH: 1.31 (1H, s), 1.35 (1H, s)). The 13C NMR spectra of 2 (Table 3) showed a total of 11 carbon resonances, and they were classified as two amide carbonyls (δC: 169.7, 166.1), three methines (δC: 70.9, 58.8, 53.2), four methylene signals (δC: 45.6, 41.1, 28.3, 22.6), two methyl signals (δC: 32.3, 27.4). Further analysis of the NMR data confirmed the existence of moieties of Pro and 4-hydroxyl-Leu. In the HMBC experiment (Figure 3), the correlations of H-3 (δH: 3.56 (2H, m)), and H-9 (δH: 4.23 (1H, d, J = 10.5 Hz)) with C-1 (δC: 166.1); H-5 (δH: 2.36 (1H, dd, J = 8.5, 2.5 Hz), 2.10 (1H, m)) and H-8 (δH: 7.66 (1H, s)) with C-6 (δC: 58.8) confirmed the planar structure for compound 2 was cyclo(Pro-4-hydroxyl-Leu). The relative stereochemistry of 2 was deduced from the NOE spectrum (Figure 3). When irradiating H-6 at δH: 4.08 and H-9 at δH: 4.23, the integration values of H-9 and H-6 were enhanced respectively, which showed that H-6 and H-9 positioned cis to each other. That is to say relative configurations of Pro and 4-hydroxyl-Leu were either l or d configurations. On the basis of Marfey’s method, the presence of l-Pro in 2 compared with the appropriate amino acid standards (Table 2, Supplementary Materials Figure S17), determined the configuration of compound 2 as cyclo(l-Pro-4-hydroxyl-l-Leu).

Bottom Line: Furthermore, the differences in NMR data of keto-enol tautomers in tirandamycins were discussed for the first time.Compound 1 exhibited moderate antibacterial activities against Staphylococcuse pidermidis, S. aureus, Enterococcus faecium, and E. faecalis with the minimum inhibitory concentration (MIC) values ranged from 16 to 64 μg/mL.Moreover, it displayed remarkable anti-tumor activities; the highest activity was observed against the Jurkat cell line (human T-cell leukemia) with an IC50 value of 0.414 μM.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Xicheng District, Beijing 100050, China. zhenxin@imm.ac.cn.

ABSTRACT
Quinomycin G (1), a new analogue of echinomycin, together with a new cyclic dipeptide, cyclo-(l-Pro-4-OH-l-Leu) (2), as well as three known antibiotic compounds tirandamycin A (3), tirandamycin B (4) and staurosporine (5), were isolated from Streptomyces sp. LS298 obtained from a marine sponge Gelliodes carnosa. The planar and absolute configurations of compounds 1 and 2 were established by MS, NMR spectral data analysis and Marfey's method. Furthermore, the differences in NMR data of keto-enol tautomers in tirandamycins were discussed for the first time. Antibacterial and anti-tumor activities of compound 1 were measured against 15 drug-sensitive/resistant strains and 12 tumor cell lines. Compound 1 exhibited moderate antibacterial activities against Staphylococcuse pidermidis, S. aureus, Enterococcus faecium, and E. faecalis with the minimum inhibitory concentration (MIC) values ranged from 16 to 64 μg/mL. Moreover, it displayed remarkable anti-tumor activities; the highest activity was observed against the Jurkat cell line (human T-cell leukemia) with an IC50 value of 0.414 μM.

Show MeSH
Related in: MedlinePlus