Rakicidins, New Cytotoxic Lipopeptides from Micromonospora sp. Fermentation, Isolation and Characterization.

Mcbrien, Kimberly D.; Berry, Ronald L.; Lowe, Susan E.; Neddermann, Kim M.; Bursuker, Isia; Huang, Stella; Klohr, Steven E.; Leet, John E.

doi:10.7164/antibiotics.48.1446

Cited by 90 publications

(117 citation statements)

References 5 publications

Supporting

Mentioning

114

Contrasting

Order By: Relevance

“…IR spectrum was measured on a PerkinElmer Spectrum 100 (PerkinElmer, Waltham, MA, USA). NMR spectra were obtained on a Bruker AVANCE 400 or a Bruker AVANCE 500 spectrometer (Bruker, Bremen, Germany) in dimethyl sulfoxide-d 6 …”

Section: Experimental Procedures General Experimental Proceduresmentioning

confidence: 99%

“…To date, three congeners, rakicidins A (2) and B (3) from Micromonospora and rakicidin C (4) from Streptomyces, have been reported. 6,7 Rakicidins contain a rare unusual amino acid, 4-amino-2,4-pentadienoate, which has been found only in the secondary metabolites from actinomycetes. Except for rakicidins, only two classes of cyclic peptides, BE43547 8 and vinylamycin, 9 are reported to date to contain this unusual amino acid.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Rakicidin D, an inhibitor of tumor cell invasion from marine-derived Streptomyces sp.

et al. 2010

View full text Add to dashboard Cite

Tumor metastasis is the leading cause of death in cancer patients. It is the process by which a tumor cell leaves the primary tumor, disseminates to a distant site through the circulatory system and establishes a secondary tumor. 1 During the metastatic cascade, tumor cells must pass through the extracellular matrix barriers to accomplish the metastasis. Although the genetic basis of tumorigenesis can vary greatly, the steps required for metastasis are similar for all tumor cells. Therefore, interruption of metastasis is a promising approach to the treatment of cancers of various genetic origins. In our continuing search for anti-invasive compounds from microbial secondary metabolites, 2-5 rakicidin D (1) was isolated from the culture broth of an actinomycete strain of the genus Streptomyces. Rakicidins are the 15-membered depsipeptides consisting of three amino acids and a 3-hydroxyfatty acid (Figure 1). To date, three congeners, rakicidins A (2) and B (3) from Micromonospora and rakicidin C (4) from Streptomyces, have been reported. 6,7 Rakicidins contain a rare unusual amino acid, 4-amino-2,4-pentadienoate, which has been found only in the secondary metabolites from actinomycetes. Except for rakicidins, only two classes of cyclic peptides, BE43547 8 and vinylamycin, 9 are reported to date to contain this unusual amino acid. Herein, we describe the isolation, structure elucidation and biological properties of rakicidin D (1).The producing strain Streptomyces sp. MWW064 was isolated from a marine sediment sample collected in Samut Sakhon province, Thailand. The strain was cultured in our standard medium for actinomycetes and the whole culture broth was extracted with 1-butanol. The extract showed inhibitory activity toward tumor cell invasion into Matrigel, the reconstituted extracellular matrix proteins. 10 Bioassay-guided fractionation of the extract led to the isolation of a new compound, rakicidin D (1).Compound 1 was obtained as a colorless amorphous powder. The high-resolution ESITOFMS indicated a molecular formula of C 24 H 38 N 4 O 7 , which was consistent with the 1 H and 13 C NMR data. The IR spectrum of 1 indicated the presence of OH or NH (3356 cm À1 ) and carbonyl (1688 and 1648 cm À1 ) functionalities. The UV spectrum and the 1 H and 13 C NMR spectra of 1 showed high similarity to those for rakicidins A and B. 7 The 13 C NMR and HMQC analysis confirmed the presence of 24 carbons attributable to six deshielded signals including carbonyl carbons, two sp 2 methines, one sp 2 methylene, five sp 3 methines, six sp 3 methylenes, four methyl carbons and five exchangeable protons.

show abstract

Section: Experimental Procedures General Experimental Proceduresmentioning

confidence: 99%

mentioning

confidence: 99%

Rakicidin D, an inhibitor of tumor cell invasion from marine-derived Streptomyces sp.

et al. 2010

View full text Add to dashboard Cite

show abstract

“…TP-A0860 was found to produce BU-4664L [1] and rakicidins [2]. BU-4664L was originally isolated from Micromonospora sp.…”

Section: Abstract Bu-4664l Antitumor Micromonosporamentioning

confidence: 99%

Revision of the Structure Assigned to the Antibiotic BU-4664L from Micromonopora

et al. 2005

View full text Add to dashboard Cite

The structure assigned to the antitumor antibiotic BU-4664L from Micromonospora sp. was revised to 5,10-dihydro-4,6,8-trihydroxy-10-(3,7,11-trimethyltrans-2,trans-6,10-dodecatrienyl)-11H-dibenzo[b,e][1,4]-diazepin-11-one based on the NMR analysis. Keywords BU-4664L, antitumor, MicromonosporaIn the screening of antitumor compounds from rare actinomycetes, Micromonospora sp. TP-A0860 was found to produce BU-4664L [1] and rakicidins [2]. BU-4664L was originally isolated from Micromonospora sp. M990-6 as a lipoxygenase inhibitor and was shown to have potent in vitro and in vivo antitumor activity. The structure of BU-4664L is described in a patent as shown ( Fig. 1). During the structural confirmation of the compounds produced by strain TP-A0860, we found that the proposed structure of BU-4664L was incorrect. We herein report the revision of the structure of BU-4664L on the basis of NMR analysis.The producing strain was isolated from a soil sample collected in Osawano, Toyama, Japan and identified as Micromonospora sp. based on the taxonomic study. Seed and production fermentation was carried out in V-22 and A-3M medium, respectively, as described previously [3]. The fermentation broth (5 liters) was extracted with 1-butanol and the organic layer was concentrated in vacuo. The oily extract (17 g)

show abstract

“…FW523-3 was dissolved in dimethyl sulfoxide solution (DMSO) (Sigma). Cells were seeded into 96-well plates at a density of 1x10 4 cells/well (in triplicate). Various concentrations of FW523-3 were added to the medium 24 h later.…”

Section: Methodsmentioning

confidence: 99%

FW523-3, a novel lipopeptide compound, induces apoptosis in cancer cells

Xie

Zhou

et al. 2011

Mol Med Report

View full text Add to dashboard Cite

Abstract. FW523-3, a new lipopeptide compound, was recently isolated and purified from the culture broth of a marine Micromonospora chalcea. FW523-3 was shown to inhibit the proliferation of certain cancer cells. However, the spectra and the underlying mechanism of its antitumor activity are unclear. In this study, the MTT and colony formation assays were employed to determine the antitumor spectra of FW523-3 and its effect on cell proliferation, respectively. Apoptosis was analyzed using DNA laddering assay and flow cytometry and the involved pathways were explored by Western blotting. Results revealed that FW523-3 exhibited cytotoxicity in a panel of tumor cell lines including esophageal squamous cell carcinoma cells (EC109), lung cancer cells (A549 and 95D), gastric cancer cells (SGC7901), uterine cervix cancer cells (HeLa) and hepatocellular carcinoma cells (HepG2). Based on these results, FW523-3 inhibited the colony formation ability of tumor cells. Moreover, FW523-3 induced apoptosis via activation of caspases 9, 7 and 3. FW523-3 also blocked the ERK and p38 signaling pathways. Taken together, we propose that FW523-3 acts as a broadspectrum antitumor drug. FW523-3 inhibits tumor cell growth and induces tumor cell apoptosis via the mitochondrial and MAPK pathways. IntroductionIn 2002, an estimated 11 million new cancer cases and 7 million cancer deaths were reported worldwide, while nearly 25 million individuals were living with cancer (1). Despite the new advances in the treatment and care of cancer patients, cancer remains a major disease that defies effective cure. Currently, the majority of cancer patients are treated with chemotherapy towards the terminal stages of various types of cancer. However, a singular drawback of a number of the existing cancer chemotherapeutics is their unwanted systemic toxicity, which may result in fatality. Therefore, new therapeutics are required for effective treatment and management of this disease. New the rapeutics with limited systemic toxicity, easier administration, longer efficacy and ability to act synergistically with existing chemotherapeutic drugs should not only improve the survival and quality of life of patients, but also be cost-effective. Thus, new drugs that are relevant to cancer chemotherapeutics are attractive candidates for investigation (2).FW523-3, a lipopeptide compound, was isolated and purified from the culture broth of a marine Micromonospora chalcea (3). Its physicochemical properties and spectra revealed that FW523-3 is identical to a known antitumor antibiotic, lipopeptide rakicidin B, which exhibited a marked cytotoxicity against the M109 cells (3,4). Results of a previous study showed that FW523-3 markedly inhibits the proliferation of K562 and L929 cells and significantly reduces the size of the F-actin volume, mitochondrial quantity and membrane transmembrane potential (3,5). These studies indicate that FW523-3 may have an antitumor bioactivity. However, the spectra and underlying mechanism of its antitumor activity have yet to be elucid...

show abstract

Rakicidins, New Cytotoxic Lipopeptides from Micromonospora sp. Fermentation, Isolation and Characterization.

Cited by 90 publications

References 5 publications

Rakicidin D, an inhibitor of tumor cell invasion from marine-derived Streptomyces sp.

Rakicidin D, an inhibitor of tumor cell invasion from marine-derived Streptomyces sp.

Revision of the Structure Assigned to the Antibiotic BU-4664L from Micromonopora

FW523-3, a novel lipopeptide compound, induces apoptosis in cancer cells

Contact Info

Product

Resources

About