17-O-Demethylgeldanamycin
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| Category | Antibiotics |
| Catalog number | BBF-00817 |
| CAS | 52762-28-4 |
| Molecular Weight | 546.61 |
| Molecular Formula | C28H38N2O9 |
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Description
17-O-Demethylgeldanamycin is an ansa antibiotic produced by Streptomyces hygroscopicus B-434. Anti-tumor activity.
Specification
| Synonyms | 17-Desmethylgeldanamycin; Des-O-methylgeldanamycin; 17-Des-O-methylgeldanamycin |
| IUPAC Name | [(4E,6Z,10E)-13,22-dihydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,19,20-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18(22)-pentaen-9-yl] carbamate |
| Canonical SMILES | CC1CC(C(C(C=C(C(C(C=CC=C(C(=O)NC2=CC(=O)C(=O)C(=C2O)C1)C)OC)OC(=O)N)C)C)O)OC |
| InChI | InChI=1S/C28H38N2O9/c1-14-10-18-24(33)19(13-20(31)25(18)34)30-27(35)15(2)8-7-9-21(37-5)26(39-28(29)36)17(4)12-16(3)23(32)22(11-14)38-6/h7-9,12-14,16,21-23,26,32-33H,10-11H2,1-6H3,(H2,29,36)(H,30,35)/b9-7-,15-8+,17-12+ |
| InChI Key | AFFSZNHAULCEKY-AFGHJBDBSA-N |
Properties
| Appearance | Purple Crystal |
| Antibiotic Activity Spectrum | neoplastics (Tumor) |
| Melting Point | 263°C |
Reference Reading
1. Biotransformation of geldanamycin and 17-allylamino-17-demethoxygeldanamycin by human liver microsomes: reductive versus oxidative metabolism and implications
Wensheng Lang, Gary W Caldwell, Jian Li, Gregory C Leo, William J Jones, John A Masucci Drug Metab Dispos. 2007 Jan;35(1):21-9. doi: 10.1124/dmd.106.009639. Epub 2006 Sep 29.
Comparative metabolite profiling of geldanamycin and 17-allylamino-17-demethoxygeldanamycin (17AAG) using human liver microsomes in normoxia and hypoxia was conducted to understand their differential metabolic fates. Geldanamycin bearing a 17-methoxy group primarily underwent reductive metabolism, generating the corresponding hydroquinone under both conditions. The formed hydroquinone resists further metabolism and serves as a reservoir. On exposure to oxygen, this hydroquinone slowly reverts to geldanamycin. In the presence of glutathione, geldanamycin was rapidly converted to 19-glutathionyl geldanamycin hydroquinone, suggesting its reactive nature. In contrast, the counterpart (17AAG) preferentially remained as its quinone form, which underwent extensive oxidative metabolism on both the 17-allylamino sidechain and the ansa ring. Only a small amount (<1%) of 19-glutathione conjugate of 17AAG was detected in the incubation of 17AAG with glutathione at 37 degrees C for 60 min. To confirm the differential nature of quinone-hydroquinone conversion between the two compounds, hypoxic incubations with human cytochrome P450 reductase at 37 degrees C and direct injection analysis were performed. Approximately 89% of hydroquinone, 5% of quinone, and 6% of 17-O-demethylgeldanamycin were observed after 1-min incubation of geldanamycin, whereas about 1% of hydroquinone and 99% of quinone were found in the 60-min incubation of 17AAG. The results provide direct evidence for understanding the 17-substituent effects of these benzoquinone ansamycins on their phase I metabolism, reactivity with glutathione, and acute hepatotoxicity.
2. [Isolation and structural elucidation of secondary metabolites from marine Streptomyces sp. SCSIO 1934]
Siwen Niu, Sumei Li, Xinpeng Tian, Tao Hu, Jianhua Ju, Xiaohong Ynag, Si Zhang, Changsheng Zhang Zhongguo Zhong Yao Za Zhi. 2011 Jul;36(13):1763-8.
Marine Actinobacteria are emerging as new resources for bioactive natural products with promise in novel drug discovery. In recent years, the richness and diversity of marine Actinobacteria from the South China Sea and their ability in producing bioactive products have been investigated. The objective of this work is to isolate and identify bioactive secondary metabolites from a marine actinobacterium SCSIO 1934 derived from sediments of South China Sea. The strain was identified as a Streptomyces spieces by analyzing its 16S rDNA sequence. Streptomyces sp. SCSIO 1934 was fermented under optimized conditions and seven bioactive secondary metabolites were isolated and purified by chromatographic methods including colum chromatography over silica gel and Sephadex LH-20. Their structures were elucidated as 17-O-demethylgeldanamycin (1), lebstatin (2), 17-O-demethyllebstatin (3), nigericin (4), nigericin sodium salt (5), abierixin (6), respectively, by detailed NMR spectroscopic data (1H, 13C, COSY, HSQC and HMBC). This work provided a new marine actinobacterium Streptomyces sp. SCSIO 1934, capable of producing diverse bioactive natural products.
3. Geldanamycin derivatives and neuroprotective effect on cultured P19-derived neurons
Sarin Tadtong, Duangdeun Meksuriyen, Somboon Tanasupawat, Minoru Isobe, Khanit Suwanborirux Bioorg Med Chem Lett. 2007 May 15;17(10):2939-43. doi: 10.1016/j.bmcl.2006.12.041. Epub 2006 Dec 15.
Geldanamycin (1), an antifungal and anticancer ansamycin, was reported as a neurotrophic and neuroprotective substance against antineoplastic drugs, paclitaxel, vincristine, and cisplatin, on cultured dorsal root ganglion neurons from chick embryos. In this study, 1 in a large quantity, together with a known 17-O-demethylgeldanamycin (2), and a new 17-O-demethylgeldanamycin hydroquinone (3) were obtained from a mangrove Streptomyces sp. A series of O-alkyl and N-alkyl derivatives of 1 were prepared by modification of C-17 and/or C-19 on the quinone ring and were evaluated for in vitro activity against P19-derived neurons. Compound 1 and 19-O-methylgeldanamycin (7) at a very low dose (1nM) enhanced survival and neurite outgrowth of P19-derived neurons and prevented neurotoxicity of paclitaxel and vinblastine. Compound 7, possessing the lowest cytotoxicity and neurotoxicity, is serving as the most promising candidate in neurodegenerative therapy against neurotoxic anticancer drugs.
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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 ╳
