Abstract
A new cytotoxic substance named mechercharmycin A was isolated from marine-derived Thermoactinomyces sp. YM3-251. The structure of mechercharmycin A was determined by an X-ray crystallographic analysis to be cyclic peptide-like and bearing four oxazoles and a thiazole. Mechercharmycin B, a linear congener of mechercharmycin A, was also isolated from the same bacterium. Mechercharmycin A exhibited relatively strong antitumor activity, whereas mechercharmycin B exhibited almost no such activity.
Article PDF
References
Blunt JW, Copp BR, Munro MHG, Northcote PT, Prinsep MR . Marine natural products. Nat Prod Rep 21: 1–49 ( 2004)
Compound 1 was reported as a cytotoxic substance in a patent during the preparation of this manuscript. Romero P, Malet L, Canedo LM, Cuevas C, Fernando RJ. New cytotoxic depsipeptides. WO 2005/000880 A2, January 6, 2005
The strain producing 1 and 2, The, has been identified as Thermoactinomyces sp. by taxonomic studies, including a 16S rDNA sequence analysis. The strain has been deposited in the NITE Patent Microorganisms Depositary (NPMD) in Japan as NITE P-2.
The B2 medium (1 liter) contained 5 g of peptone, 1 g of yeast extract, 1.1 g of iron (III) citrate n-hydrate, 750 ml of filtered natural sea water, and 250 ml of distilled water (pH 7.6, before sterilization).
Shin-ya K, Wierzba K, Matsuo K, Ohtani T, Yamada Y, Furihata K, Hayakawa Y, Seto H . Telomestatin, a novel telomerase inhibitor from Streptomyces anulatus. J Am Chem Soc 123: 1262–1263 ( 2001)
The crystal used for the X-ray crystallographic analysis contained sodium methoxide. Crystal data for 1: C36H35N8NaO8S, colorless cube, Mr=762.768, triclinic P $$\overline{1}$$, a=11.7380(8) Å, b=12.9590(11) Å, c=13.1900(10) Å, α=89.999(6)°, β=90.062(7)°, γ=110.351(3)°, V=1881.1(2) Å3, Z=2, ρcalcd=1.322 mg m−3, μ=0.158 mm−1, T=298 K, 9879 measured reflections, 9879 independent reflections, 973 parameters, GOF=1.005, R1(wR2)=0.0495(0.1367). The measurements were carried out on Mac Science (Bruker Nonius) dip image plate diffractometer using graphite-monochromated MoKα radiation (λ=071073 Å). The crystal structure was solved by the direct method with SIR-97. Refinement was performed by a full matrix least squares refinement on F2 with SHELXL-97. CCDC 262340 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre viawww.ccdc.cam.ac.uk/data_request/cif.
Marfey P . Determination of D-amino acids. II. Use of a bifunctional reagent, 1,5-difluoro-2,4-dinitrobenzene. Carlsberg Res Commun 49: 591–596, 1984
A549 cells were cultured in a DMEM medium containing 10% fetal bovine serum. The cells were seeded in a 96-well microplate (4,000 cells/200 ml/well) and then cultured in a CO2 incubator (5% CO2 - air, 37°C) for 14 hours. Serially diluted samples were added to each well, and the cells were cultured for a further 48 hours. The cell number was counted by the Alamar BlueTM method, and the IC50 value was determined from three independent experiments. Jurkat cells were cultured in an RPMI 1640 medium containing 10% fetal bovine serum. The IC50 value for the Jurkat cells was determined by the same procedure as that used for the A549 cells. The IC50 value of staurosporine for the A549 cells was 3.5×10−8 M, and for the Jurkat cells was 1.5×10−8 M.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kanoh, K., Matsuo, Y., Adachi, K. et al. Mechercharmycins A and B, Cytotoxic Substances from Marine-derived Thermoactinomyces sp. YM3-251. J Antibiot 58, 289–292 (2005). https://doi.org/10.1038/ja.2005.36
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ja.2005.36
Keywords
This article is cited by
-
The intriguing chemistry and biology of sulfur-containing natural products from marine microorganisms (1987–2020)
Marine Life Science & Technology (2021)