Leucinostatin B
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| Category | Antibiotics |
| Catalog number | BBF-02252 |
| CAS | 76663-52-0 |
| Molecular Weight | 1204.58 |
| Molecular Formula | C61H109N11O13 |
| Purity | >95% |
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Description
It is produced by the strain of Paecilomyces lilacinus A-267. It's a peptide antibiotic. It has a strong anti-pathogenic and non-pathogenic yeast and fungi activity, but also has a medium anti-bacterial effect. It was previously reported that Leucinostatin A and B mixtures inhibited HeLa cells. 0.05 μg/mL of Leucinostatin B for a week (0.25 mg/kg・d) has inhibitory effect on the airy ascites carcinoma entity type, and for ascites type is invalid.
Specification
| Related CAS | 88929-99-1 (hydrochloride) |
| Synonyms | Paecilotoxin B; Leucinostatin A, 9-[N-[1-methyl-2-(methylamino)ethyl]-b-alaninamide]-, [9(S)]-; Antibiotic 1907-II; b-Alaninamide, cis-4-methyl-1-(4-methyl-1-oxo-2-hexenyl)-L-prolyl-(4S,6S)-6-hydroxy-4-methyl-8-oxo-L-2-aminodecanoyl-threo-3-hydroxy-L-leucyl-2-methylalanyl-L-leucyl-L-leucyl-2-methylalanyl-2-methylalanyl-N-[1-methyl-2-(methylamino)ethyl]-, [1[S-(E)],9(S)]- |
| IUPAC Name | (2S,4S)-N-[(2R,4S,6S)-6-hydroxy-1-[[(2S,3R)-3-hydroxy-4-methyl-1-[[2-methyl-1-[[(2S)-4-methyl-1-[[(2S)-4-methyl-1-[[2-methyl-1-[[2-methyl-1-[[3-[[(2S)-1-(methylamino)propan-2-yl]amino]-3-oxopropyl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopentan-2-yl]amino]-4-methyl-1,8-dioxodecan-2-yl]-4-methyl-1-[(E,4R)-4-methylhex-2-enoyl]pyrrolidine-2-carboxamide |
| Canonical SMILES | CCC(C)C=CC(=O)N1CC(CC1C(=O)NC(CC(C)CC(CC(=O)CC)O)C(=O)NC(C(C(C)C)O)C(=O)NC(C)(C)C(=O)NC(CC(C)C)C(=O)NC(CC(C)C)C(=O)NC(C)(C)C(=O)NC(C)(C)C(=O)NCCC(=O)NC(C)CNC)C |
| InChI | InChI=1S/C61H109N11O13/c1-20-37(9)22-23-48(76)72-33-39(11)30-46(72)54(81)66-45(29-38(10)28-42(74)31-41(73)21-2)52(79)68-49(50(77)36(7)8)55(82)70-60(15,16)57(84)67-43(26-34(3)4)51(78)65-44(27-35(5)6)53(80)69-61(17,18)58(85)71-59(13,14)56(83)63-25-24-47(75)64-40(12)32-62-19/h22-23,34-40,42-46,49-50,62,74,77H,20-21,24-33H2,1-19H3,(H,63,83)(H,64,75)(H,65,78)(H,66,81)(H,67,84)(H,68,79)(H,69,80)(H,70,82)(H,71,85)/b23-22+/t37-,38-,39+,40+,42+,43+,44+,45-,46+,49+,50-/m1/s1 |
| InChI Key | JLDCSWRYRVBFRU-YHHRVAAASA-N |
Properties
| Appearance | Amorphous Powder |
| Antibiotic Activity Spectrum | Neoplastics (Tumor); Fungi; Yeast |
| Boiling Point | 1414.2°C at 760 mmHg |
| Melting Point | 132-140°C |
| Density | 1.119 g/cm3 |
| Solubility | Soluble in Methanol, Ethanol |
Reference Reading
1. Leucinostatins from Ophiocordyceps spp. and Purpureocillium spp. Demonstrate Selective Antiproliferative Effects in Cells Representing the Luminal Androgen Receptor Subtype of Triple Negative Breast Cancer
Yun-Seo Kil, April L Risinger, Cora L Petersen, Susan L Mooberry, Robert H Cichewicz J Nat Prod. 2020 Jun 26;83(6):2010-2024. doi: 10.1021/acs.jnatprod.0c00404. Epub 2020 Jun 8.
The structures of four leucinostatin analogues (1-4) from Ophiocordyceps spp. and Purpureocillium spp. were determined together with six known leucinostatins [leucinostatins B (5), A (6), B2 (7), A2 (8), F (9), and D (10)]. The structures of the metabolites were established using a combination of analytical methods including HRESIMS and MS/MS experiments, 1D and 2D NMR spectroscopy, chiral HPLC, and advanced Marfey's analysis of the acid hydrolysate, as well as additional empirical and chemical methods. Compounds 1-10 were evaluated for their biological effects on triple negative breast cancer (TNBC) cells. Leucinostatins 1-10 showed selective cytostatic activities in MDA-MB-453 and SUM185PE cells representing the luminal androgen receptor subtype of TNBC. This selective activity motivated further investigation into the mechanism of action of leucinostatin B (5). The results demonstrate that this peptidic fungal metabolite rapidly inhibits mTORC1 signaling in leucinostatin-sensitive TNBC cell lines, but not in leucinostatin-resistant cells. Leucinostatins have been shown to repress mitochondrial respiration through inhibition of the ATP synthase, and we demonstrated that both the mTORC1 signaling and LAR-selective activities of 5 were recapitulated by oligomycin. Thus, inhibition of the ATP synthase with either leucinostatin B or oligomycin is sufficient to selectively impede mTORC1 signaling and inhibit the growth of LAR-subtype cells.
2. In vitro and in vivo antitrypanosomal activities of three peptide antibiotics: leucinostatin A and B, alamethicin I and tsushimycin
Aki Ishiyama, Kazuhiko Otoguro, Masato Iwatsuki, Miyuki Namatame, Aki Nishihara, Kenichi Nonaka, Yuta Kinoshita, Yoko Takahashi, Rokuro Masuma, Kazuro Shiomi, Haruki Yamada, Satoshi Omura J Antibiot (Tokyo). 2009 Jun;62(6):303-8. doi: 10.1038/ja.2009.32. Epub 2009 May 1.
In the course of our screening for antitrypanosomal compounds from soil microorganisms, as well as from the antibiotics library of the Kitasato Institute for Life Sciences, we found three peptide antibiotics, leucinostatin (A and B), alamethicin I and tsushimycin, which exhibited potent or moderate antitrypanosomal activity. We report here the in vitro and in vivo antitrypanosomal properties and cytotoxicities of leucinostatin A and B, alamethicin I and tsushimycin compared with suramin. We also discuss their possible mode of action. This is the first report of in vitro and in vivo trypanocidal activity of leucinostatin A and B, alamethicin I and tsushimycin.
3. Identification of Leucinostatins from Ophiocordyceps sp. as Antiparasitic Agents against Trypanosoma cruzi
Jean A Bernatchez, Yun-Seo Kil, Elany Barbosa da Silva, Diane Thomas, Laura-Isobel McCall, Karen L Wendt, Julia M Souza, Jasmin Ackermann, James H McKerrow, Robert H Cichewicz, Jair L Siqueira-Neto ACS Omega. 2022 Jan 28;7(9):7675-7682. doi: 10.1021/acsomega.1c06347. eCollection 2022 Mar 8.
Safe and effective treatments for Chagas disease, a potentially fatal parasitic infection associated with cardiac and gastrointestinal pathology and caused by the kinetoplastid parasite Trypanosoma cruzi, have yet to be developed. Benznidazole and nifurtimox, which are currently the only available drugs against T. cruzi, are associated with severe adverse effects and questionable efficacy in the late stage of the disease. Natural products have proven to be a rich source of new chemotypes for other infectious agents. We utilized a microscopy-based high-throughput phenotypic screen to identify inhibitors of T. cruzi from a library of natural product samples obtained from fungi procured through a Citizen Science Soil Collection Program (https://whatsinyourbackyard.org/) and the Great Lakes (USA) benthic environment. We identified five leucinostatins (A, B, F, NPDG C, and NPDG D) as potent inhibitors of the intracellular amastigote form of T. cruzi. Leucinostatin B also showed in vivo suppression of T. cruzi in a mouse model of Chagas disease. Given prior reports that leucinostatins A and B have antiparasitic activity against the related kinetoplastid Trypanosoma brucei, our findings suggest a potential cross-trypanocidal compound class and provide a platform for the further chemical derivatization of a potent chemical scaffold against T. cruzi.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
