108102-51-8Relevant articles and documents
Ligerin, an antiproliferative chlorinated sesquiterpenoid from a marine-derived penicillium strain
Vansteelandt, Marieke,Blanchet, Elodie,Egorov, Maxim,Petit, Fabien,Toupet, Loic,Bondon, Arnaud,Monteau, Fabrice,Bizec, Bruno,Thomas, Olivier P.,Pouchus, Yves Francois,Bot, Ronan Le,Grovel, Olivier
, p. 297 - 301 (2013)
A new chlorinated sesquiterpenoid analogue of fumagillin, ligerin (1), was isolated from a marine-derived strain of Penicillium, belonging to the subgenus Penicillium, along with the known compounds penicillic acid (2), orcinol, and orsellinic acid. Chemical structures were established by an interpretation of spectroscopic data including IR, UV, and HRESIMS, together with analyses of 1D and 2D NMR spectra and X-ray analysis for the determination of the absolute configuration. Ligerin (1) displayed strong inhibitory activity against an osteosarcoma cell line. This is the first report of the isolation of a fumagillin analogue from a marine-derived Penicillium strain.
RK-805, an endothelial-cell-growth inhibitor produced by Neosartorya sp., and a docking model with methionine aminopeptidase-2
Asami, Yukihiro,Kakeya, Hideaki,Onose, Rie,Chang, Yie-Hwa,Toi, Masakazu,Osada, Hiroyuki
, p. 7085 - 7091 (2004)
We found that a fungus Neosartorya sp. produced an angiogenesis inhibitor, RK-805. By spectroscopic analyses and semi-synthetic methods from fumagillin, the structure of RK-805 was identified as 6-oxo-6-deoxyfumagillol, which has not been reported as a natural product. RK-805 preferentially inhibited the growth of human umbilical vein endothelial cells (HUVECs) rather than that of human normal fibroblast in cell proliferation assays and blocked endothelial cell migration induced by vascular endothelial growth factor (VEGF). Moreover, RK-805 selectively inhibited methionine aminopeptidase-2 (MetAP2), but not methionine aminopeptidase-1 (MetAP1). The docked structure of RK-805 complexed with human MetAP2 indicated that not only a covalent bond between a nucleophilic imidazole nitrogen atom of His231 and the carbon of the reactive spirocyclic epoxide of RK-805, but also a hydrogen bond between NH (Asn329) and the carbonyl group of RK-805 at C-6 promote close contact in the binding pocket of the enzyme. Taken together, these results suggest that structure activity relationships of RK-805 derivatives at both C-4 and C-6, in comparison with ovalicin and TNP-470, would be useful for development of new angiogenesis inhibitors.
FUMAGILLOL DERIVATIVES
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Paragraph 0159-0160, (2016/07/05)
Disclosed are compounds of Formula (1), stereoisomers thereof and pharmaceutically acceptable salts of the compounds and stereoisomers, wherein R1 and R2 are defined in the specification. This disclosure also relates to materials and
Synthesis and antiproliferative activity of ligerin and new fumagillin analogs against osteosarcoma
Blanchet, Elodie,Vansteelandt, Marieke,Le Bot, Ronan,Egorov, Maxim,Guitton, Yann,Pouchus, Yves Fran?ois,Grovel, Olivier
, p. 244 - 250 (2014/05/06)
Ligerin (1) is a natural chlorinated merosesquiterpenoid related to fumagillin (2) exhibiting a selective antiproliferative activity against osteosarcoma cell lines and an in vivo antitumor activity in a murine model. Semisynthesis of ligerin analogs was performed in order to study the effects of the C3-spiroepoxide substitution by a halogenated moiety together with the modulation of the C6 chain. Results showed that all derivatives exhibited an in vitro antiproliferative activity against osteosarcoma cell lines and that chlorohydrin compounds were equally or more active than their spiroepoxy analogs. Among semisynthetic analogs, the parent compound 1 was the best candidate for further studies since it exhibited higher or equivalent activity compared to TNP470 (3) against SaOS2 and MG63 human osteosarcoma cells with a four times weaker toxicity against HFF2 human fibroblasts. Quantitative videomicroscopy analysis was conducted and allowed a better understanding of the mechanism of its antiproliferative activity.
