ABSTRACT
2-Methylthio-N7-methyl-cis-zeatin (1) was isolated from the culture broth of Streptomyces sp. 80H647 along with 2 known purine derivatives, 5'-methylthioinosine (2) and AT-265 (dealanylascamycin, 3). The structure elucidation of compound 1 was accomplished by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) analyses. It inhibited the growth of Plasmodium falciparum 3D7 with a GI50 of 2.4 µm and had no effect on the growth of Arabidopsis at 2 µm. This is the first report of an N7-methylated zeatin-type natural product from Streptomyces and as an antimalarial compound.
Subject(s)
AntimalarialsABSTRACT
N-acetyl-α-hydroxy-ß-oxotryptamine (1) along with N-acetyl-ß-oxotryptamine (2) and pimprinine (3) were isolated from the culture broth of Streptomyces sp. 80H647. Compound 1 was found to be a racemate via X-ray diffraction analysis and the enantiomers were successfully purified by chiral-phase HPLC. The absolute configuration was assigned by comparison of the calculated and experimental ECD spectra. The α-hydroxy moiety of 1 was vital for cytotoxicity against different cancer cell lines.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Biological Products/chemistry , Streptomyces/chemistry , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Biological Products/pharmacology , Cell Line, Tumor , Crystallography, X-Ray , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , Magnetic Resonance Spectroscopy , Molecular Structure , Stereoisomerism , Structure-Activity Relationship , Tryptamines/chemistryABSTRACT
A new siderophore glucuronide, nocardamin glucuronide (1), was isolated together with nocardamin (2) by applying the one strain-many compounds (OSMAC) approach to the ascamycin-producing strain, Streptomyces sp. 80H647, and performing multivariate analysis using mass spectral data. Structure elucidation was accomplished by a combination of NMR and MS analyses. The absolute configuration of the glucuronic acid moiety was found to be ß-D-GlcA by hydrolysis using ß-glucuronidase, subsequent derivatization of the hydrolysate, and comparison with standards. The siderophore activity of 1 was evaluated through the chrome azurol S assay and was comparable to that of 2 and deferoxamine (IC50 13.4, 9.5, and 6.3 µM, respectively). Nocardamin glucuronide (1) is the first example of a siderophore glucuronide.
Subject(s)
Siderophores/chemistry , Siderophores/pharmacology , Streptomyces/metabolism , Adenosine/analogs & derivatives , Adenosine/metabolism , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antimalarials/chemistry , Antimalarials/pharmacology , Cell Line, Tumor , Deferoxamine/pharmacology , Humans , Hydroxybenzoates/chemistry , Iron/metabolism , Magnetic Resonance Spectroscopy , Mass Spectrometry/statistics & numerical data , Molecular Structure , Peptides, Cyclic/isolation & purification , Principal Component Analysis , Siderophores/isolation & purification , Siderophores/toxicity , Toxicity TestsABSTRACT
NMR- and MS-guided fractionation of an extract of an Okeania sp. marine cyanobacterium, collected from the Red Sea, led to the isolation of four new metabolites, including serinolamides C (1) and D (2) and lyngbyabellins O (3) and P (4), together with the three known substances lyngbyabellins F (5) and G (6) and dolastatin 16 (7). The planar structures of the new compounds were determined using NMR and MS analyses. The absolute configurations of 1 and 2 were determined by Marfey's analysis of their hydrolysates. The absolute configuration of 3 was ascertained by chiral-phase chromatography of degradation products, while that of 4 was determined by comparison to 3 and 5. The cytotoxic and antifouling activities of these compounds were evaluated using MCF7 breast cancer cells and Amphibalanus amphitrite larvae, respectively. Compounds 3, 4, and 7 exhibited strong antifouling activity, and 3 and 7 were not cytotoxic. A structure-activity relationship was observed for the cytotoxicity of the lyngbyabellins with the presence of a side chain (4 is more active than 3) leading to greater activity. For the antifouling activity, the acyclic form without a side chain (3) was the most active.
Subject(s)
Cyanobacteria/chemistry , Depsipeptides/isolation & purification , Lipids/isolation & purification , Animals , Biofouling/prevention & control , Breast Neoplasms , Depsipeptides/chemistry , Depsipeptides/pharmacology , Drug Screening Assays, Antitumor , Female , Humans , Indian Ocean , Lipids/chemistry , Lipids/pharmacology , Marine Biology , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Structure-Activity Relationship , Thoracica/chemistryABSTRACT
Two new chlorinated fatty acid amides, columbamides D (1) and E (2), along with apratoxins A and C and wewakazole, were isolated from the organic extract of a Moorea bouillonii sample from Sabah, Malaysia. Structure elucidation was accomplished by a combination of MS and NMR analyses. The total synthesis of all four stereoisomers of 1 was completed, and the absolute configuration was determined by chiral-phase HPLC and Marfey's analysis.
Subject(s)
Amides/isolation & purification , Cyanobacteria/chemistry , Fatty Acids/isolation & purification , Amides/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Aquatic Organisms , Cell Line, Tumor , Drug Screening Assays, Antitumor/methods , Fatty Acids/chemistry , Halogenation , Humans , Malaysia , Molecular Conformation , Peptides, Cyclic/chemistry , Peptides, Cyclic/isolation & purification , StereoisomerismABSTRACT
A mass spectrometry (MS)-guided isolation has led to the purification of a new cyanobactin, wewakazole B (1), along with the known compound curacin D from a Red Sea Moorea producens. The planar structure of 1 was elucidated using a combination of NMR and MS techniques. After ozonolysis and acid hydrolysis, the absolute configurations of the amino acid components of 1 were determined by chiral-phase LC-MS and HPLC analyses. Notably, compound 1 exhibited cytotoxic activity toward human MCF7 breast cancer cells (IC50 = 0.58 µM) and human H460 lung cancer cells (IC50 = 1.0 µM) and was also found to be inactive in a siderophore assay.
