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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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Structures of the isolated compounds 1–5 and reference compound echinomycin.
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marinedrugs-13-06947-f001: Structures of the isolated compounds 1–5 and reference compound echinomycin.

Mentions: The strain LS298 was obtained from a marine sponge Gelliodes carnosa collected from the South China Sea. Based on the 16S rRNA sequence (GenBank accession number FJ937945) analysis [9] and the morphology, this strain was preliminarily identified as Streptomyces sp. Our previous studies have shown that the secondary metabolites of this strain contain echinomycin, cyclic dipeptides, and esters [10]. Among these compounds, echinomycin, a bifunctional DNA intercalator, is the predominantly and biologically active constituent against the Gram-positive and Gram-negative bacteria and also shows good anti-tumor activity [11,12,13,14]. Our continued search for echinomycin analogues or other novel antibiotics from extracts of large scale fermentation led to the isolation of two new compounds quinomycin G (1) and cyclo-(l-Pro-4-OH-l-Leu) (2), as well as three known compounds tirandamycin A (3), tirandamycin B (4), and staurosporine (5) (Figure 1). Structurally, quinomycin G (1) possessed a terminal double bond in one of the Ser groups. Cyclo-(l-Pro-4-OH-l-Leu) (2) was a new cyclic dipeptide. Tirandamycin A (3) was the 1-enol-4′-keto form, while tirandamycin B (4) was 1-keto-4′-enol form. It is the first time to reveal this form of tirandamycin B explicitly. In addition, antibacterial and anti-tumor activities of compound 1 were evaluated against 15 drug-resistant/sensitive strains and 12 tumor cell lines.


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)

Structures of the isolated compounds 1–5 and reference compound echinomycin.
© Copyright Policy
Related In: Results  -  Collection

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

marinedrugs-13-06947-f001: Structures of the isolated compounds 1–5 and reference compound echinomycin.
Mentions: The strain LS298 was obtained from a marine sponge Gelliodes carnosa collected from the South China Sea. Based on the 16S rRNA sequence (GenBank accession number FJ937945) analysis [9] and the morphology, this strain was preliminarily identified as Streptomyces sp. Our previous studies have shown that the secondary metabolites of this strain contain echinomycin, cyclic dipeptides, and esters [10]. Among these compounds, echinomycin, a bifunctional DNA intercalator, is the predominantly and biologically active constituent against the Gram-positive and Gram-negative bacteria and also shows good anti-tumor activity [11,12,13,14]. Our continued search for echinomycin analogues or other novel antibiotics from extracts of large scale fermentation led to the isolation of two new compounds quinomycin G (1) and cyclo-(l-Pro-4-OH-l-Leu) (2), as well as three known compounds tirandamycin A (3), tirandamycin B (4), and staurosporine (5) (Figure 1). Structurally, quinomycin G (1) possessed a terminal double bond in one of the Ser groups. Cyclo-(l-Pro-4-OH-l-Leu) (2) was a new cyclic dipeptide. Tirandamycin A (3) was the 1-enol-4′-keto form, while tirandamycin B (4) was 1-keto-4′-enol form. It is the first time to reveal this form of tirandamycin B explicitly. In addition, antibacterial and anti-tumor activities of compound 1 were evaluated against 15 drug-resistant/sensitive strains and 12 tumor cell lines.

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