Demethyl Mutactimycins, New Anthracycline Antibiotics from Nocardia and Streptomyces Strains.

Speitling, Michael; Nattewan, P.; Yazawa, Kazunaga; Mikami, Yuzuru; Grün-Wollny, Iris; Ritzau, Michael; Laatsch, Hartmut; Gräfe, U.

doi:10.7164/antibiotics.51.693

Cited by 17 publications

(20 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Its physico-chemical properties are summarized in Table 2. 1 displayed moderate antimicrobial activity against an internal panel of pathogens, which is in good agreement with the bioactivity reported for other mutactimycins [3,4]. It is also reported that several other members of this group exhibit antiviral activity [3].…”

supporting

confidence: 84%

“…NMR data for the remaining aglycone resonances were consistent with those of other mutactimycins [3,4]. The stereochemistry at C-7 and C-9 were established as shown based on comparison with literature values [4]. An NOE experiment revealed the relative stereochemistry at C-8 via a correlation between H- 8 and the methyl group at C-9.…”

supporting

confidence: 69%

“…HMBC correlations from the latter to d 135.7 (C-6a) and d 70.1 (C-9) and a COSY correlation to a doublet at d 4.90 (H-7) confirm the presence of a hydroxyl group at C-8. NMR data for the remaining aglycone resonances were consistent with those of other mutactimycins [3,4]. The stereochemistry at C-7 and C-9 were established as shown based on comparison with literature values [4].…”

supporting

confidence: 68%

“…An HMBC correlation was observed between a methyl group at d 3.26 (H-3-O-Me) and H-3Ј on the sugar thus establishing the position of the methoxy group. Additional examination of the NMR data and comparison with literature values allowed us to identify the sugar moiety as a 6-deoxy-3-O-methyl-a -mannopyranoside [3,4]. An HMBC correlation was observed between the anomeric proton at d 5.19 (H-1Ј) and a carbon at d 74.9 (C-7) (Fig.…”

mentioning

confidence: 93%

See 3 more Smart Citations

Mutactimycin E, a New Anthracycline Antibiotic with Gram-positive Activity

Hopp¹,

Rabenstein²,

Rhea³

et al. 2008

J Antibiot

View full text Add to dashboard Cite

Resistance to currently available antibiotics has become a widely recognized crisis in the medical community. To address this, many companies and researchers are refocusing their attention towards natural products, which have an excellent track record of producing effective antibacterial drugs. The AMRI natural product library was screened for activity against multi-drug resistant Staphylococcus aureus (MDRSA). The active samples were counter screened for cytotoxicity against the human hepatocellular carcinoma HepG2 cell line to determine an in vitro therapeutic index (in vitro TI). Those samples with a high in vitro TI were selected for fractionation and dereplication. This led to the discovery of a new anthracycline structure. This metabolite, named mutactimycin E (1), exhibited moderate activity against several gram positive organisms. Here we report the isolation, structure elucidation and biological activities of this new compound. Keywords mutactimycin, anthracycline, antibiotic, AmycolatopsisIt has been known for some time that resistance to existing antibiotics is increasing. This is particularly true in hospital settings, but is also found in community-acquired infections. This development, when coupled with the decision by many pharmaceutical companies to abandon antibacterial research in the 1980's and 1990's, resulted in the absence of new antibiotics to combat current resistance mechanisms. In an effort to address this urgent need, we began a screening campaign to identify novel antibiotics from our natural product library. Natural products, particularly those produced by microbial fermentation, were the direct source or inspiration for almost all antibiotics used today and remain the richest source for new antibacterial compound series. Our extensive library consisting of over 280,000 samples was screened for activity against a multi-drug resistant strain of Staphylococcus aureus (ATCC 43300). The hits arising out of this assay were then tested against the human hepatocellular carcinoma cell line HepG2 to filter out those samples where activity was the result of general cytotoxicity. The resulting subset of samples possessing selectivity for the bacterial target were then fractionated on an HPLC system employing UV, evaporative light scattering, and MS detectors. The eluted fractions were collected into 96-well microtiter plates and submitted for bioassay. Active compounds were subsequently dereplicated on the basis of MS and UV data.One of the hits resulting from our efforts originated from the EtOAc extract of Amycolatopsis strain 17128. A scaledup fermentation of the active strain and subsequent purification of the active compound by reverse phase HPLC yielded mutactimycin E (1) as an orange solid (Fig. 1). LC/MS data for 1 indicated a molecular weight of 560 Daltons. This piece of information along with the UV spectrum was used to search internal and external databases [1]. Analysis of the hits from this search indicated

show abstract

supporting

confidence: 84%

supporting

confidence: 69%

supporting

confidence: 68%

mentioning

confidence: 93%

See 2 more Smart Citations

Mutactimycin E, a New Anthracycline Antibiotic with Gram-positive Activity

Hopp¹,

Rabenstein²,

Rhea³

et al. 2008

J Antibiot

View full text Add to dashboard Cite

show abstract

“…7) Komodoquinones A (1) and B (2) are characterized as a rare anthracycline having a 9-methyl substituent (e.g. nogalamycin, 8) steffinomycin, 9) and mutactimycin 10) ). The absolute stereo-structure of komodoquinone B (2) with 7,9-syn-dihydroxyl groups has been confirmed by application of the modified Mosher's method.…”

mentioning

confidence: 99%

Stereostructure of Komodoquinone A, a Neuritogenic Anthracycline, from Marine Streptomyces sp. KS3

Ito

Kinoshita

Wang

et al. 2003

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

The absolute stereostructure of komodoquinone A (1), a neuritogenic anthracycline, which was isolated from a cultured marine Streptomyces sp. KS3, has been determined on the basis of chemical derivatization. Komodoquinone A (1) induces neuronal cell differentiation in the neuroblastoma cell line, Neuro 2A and arrests the cell cycle at the G1 phase. The effect of a solid-state medium on the production of 1 and its aglycone, komodoquinone B (2), was examined.Key words komodoquinone A; anthracycline; Neuro 2A; marine; Streptomyces sp.; neuritogenic activity

show abstract

ChemInform Abstract: Demethyl Mutactimycins, New Anthracycline Antibiotics from Nocardia and Steptomyces Strains.

et al. 1999

View full text Add to dashboard Cite

Demethyl Mutactimycins, New Anthracycline Antibiotics from Nocardia and Steptomyces Strains. -The isolated title compound (Ia) shows moderate activity against Gram positive bacteria and also cytotoxicity against P388, L1210 and HeLa tumor cells. -(SPEITLING, M.; NATTE-WAN, P.; YAZAWA, K.; MIKAMI, Y.; GRUEN-WOLLNY, I.; RITZAU, M.; LAATSCH, H.; GRAEFE, U.; J. Antibiot. 51 (1998) 8, 693-698; Res. Cent.

show abstract

Demethyl Mutactimycins, New Anthracycline Antibiotics from Nocardia and Streptomyces Strains.

Cited by 17 publications

References 9 publications

Mutactimycin E, a New Anthracycline Antibiotic with Gram-positive Activity

Mutactimycin E, a New Anthracycline Antibiotic with Gram-positive Activity

Stereostructure of Komodoquinone A, a Neuritogenic Anthracycline, from Marine Streptomyces sp. KS3

ChemInform Abstract: Demethyl Mutactimycins, New Anthracycline Antibiotics from Nocardia and Steptomyces Strains.

Contact Info

Product

Resources

About