Streptonigrin
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
| Category | Antibiotics |
| Catalog number | BBF-00591 |
| CAS | 3930-19-6 |
| Molecular Weight | 506.46 |
| Molecular Formula | C25H22N4O8 |
| Purity | >95% by HPLC |
Online Inquiry
Description
Bruneomycin is a benzoquinone antibiotic produced by Auiw-myces albus van bruneomycini and Act. echinatus. It has anti-gram-positive bacteria, negative bacteria, and mycobacterial activity. It has inhibitory effect on lymphosarcoma Lio-1, lymphocytic leukemia NK/L1 and L-5178, Ehrlich ascites carcinoma, sarcoma-180, and has inhibitory effect on sarcoma-37 invalid.
Specification
| Synonyms | Bruneomycin; Rufocromomycin; Nigrin; Streptonigran |
| Storage | -20°C |
| IUPAC Name | 5-amino-6-(7-amino-6-methoxy-5,8-dioxoquinolin-2-yl)-4-(2-hydroxy-3,4-dimethoxyphenyl)-3-methylpyridine-2-carboxylic acid |
| Canonical SMILES | CC1=C(C(=C(N=C1C(=O)O)C2=NC3=C(C=C2)C(=O)C(=C(C3=O)N)OC)N)C4=C(C(=C(C=C4)OC)OC)O |
| InChI | InChI=1S/C25H22N4O8/c1-9-14(10-6-8-13(35-2)23(36-3)20(10)30)15(26)19(29-17(9)25(33)34)12-7-5-11-18(28-12)22(32)16(27)24(37-4)21(11)31/h5-8,30H,26-27H2,1-4H3,(H,33,34) |
| InChI Key | PVYJZLYGTZKPJE-UHFFFAOYSA-N |
| Source | Streptomyces sp. |
Properties
| Appearance | Brown Powder |
| Antibiotic Activity Spectrum | Gram-positive bacteria; Gram-negative bacteria; mycobacteria; neoplastics (Tumor) |
| Boiling Point | 719°C at 760 mmHg |
| Melting Point | 275°C(dec.) |
| Density | 1.54 g/cm3 |
| Solubility | Soluble in DMF, DMSO, methanol, ethanol |
Reference Reading
1. Interaction of streptonigrin with metals and with DNA
K V Rao J Pharm Sci . 1979 Jul;68(7):853-6. doi: 10.1002/jps.2600680717.
The antitumor antibiotic, streptonigrin, interacted with zinc, copper, and manganese but not with calcium or magnesium, as indicated by spectral shifts and difference spectra. The titration data showed the formation of 1:1 complexes, and further titration continued to show spectral shifts until a molar ratio for zinc to streptonigrin of 5-10 to 1 was reached. Streptonigrin interacted with DNA only in the presence of a metal ion such as zinc. Streptonigrin titration with DNA at varying zinc molar equivalents revealed that one antibiotic molecule required 5-7 moles of zinc and 20-25 moles of DNA-phosphorus for complexation. Similar values were obtained from gel permeation chromatography.
2. Streptonigrin at low concentration promotes heterochromatin formation
Willis X Li, Robin Shang, Kevin Dao, Andre C Loyola, Cody Fowler, Lin Zhang, Pranabananda Dutta, Jinghong Li Sci Rep . 2020 Feb 26;10(1):3478. doi: 10.1038/s41598-020-60469-6.
Heterochromatin is essential for regulating global gene transcription and protecting genome stability, and may play a role in tumor suppression. Drugs promoting heterochromatin are potential cancer therapeutics but very few are known. In order to identify drugs that can promote heterochromatin, we used a cell-based method and screened NCI drug libraries consisting of oncology drugs and natural compounds. Since heterochromatin is originally defined as intensely stained chromatin in the nucleus, we estimated heterochromatin contents of cells treated with different drugs by quantifying the fluorescence intensity of nuclei stained with Hoechst DNA dye. We used HeLa cells and screened 231 FDA-approved oncology and natural substance drugs included in two NCI drug libraries representing a variety of chemical structures. Among these drugs, streptonigrin most prominently caused an increase in Hoechst-stained nuclear fluorescence intensity. We further show that streptonigrin treated cells exhibit compacted DNA foci in the nucleus that co-localize with Heterochromatin Protein 1 alpha (HP1α), and exhibit an increase in total levels of the heterochromatin mark, H3K9me3. Interestingly, we found that streptonigrin promotes heterochromatin at a concentration as low as one nanomolar, and at this concentration there were no detectable effects on cell proliferation or viability. Finally, in line with a previous report, we found that streptonigrin inhibits STAT3 phosphorylation, raising the possibility that non-canonical STAT function may contribute to the effects of streptonigrin on heterochromatin. These results suggest that, at low concentrations, streptonigrin may primarily enhance heterochromatin formation with little toxic effects on cells, and therefore might be a good candidate for epigenetic cancer therapy.
3. Insights into the mechanism of streptonigrin-induced protein arginine deiminase inactivation
Christina J Dreyton, Erin D Anderson, Dale L Boger, Paul R Thompson, Venkataraman Subramanian Bioorg Med Chem . 2014 Feb 15;22(4):1362-9. doi: 10.1016/j.bmc.2013.12.064.
Protein citrullination is just one of more than 200 known PTMs. This modification, catalyzed by the protein arginine deiminases (PADs 1-4 and PAD6 in humans), converts the positively charged guanidinium group of an arginine residue into a neutral ureido-group. Given the strong links between dysregulated PAD activity and human disease, we initiated a program to develop PAD inhibitors as potential therapeutics for these and other diseases in which the PADs are thought to play a role. Streptonigrin which possesses both anti-tumor and anti-bacterial activity was later identified as a highly potent PAD4 inhibitor. In an effort to understand why streptonigrin is such a potent and selective PAD4 inhibitor, we explored its structure-activity relationships by examining the inhibitory effects of several analogues that mimic the A, B, C, and/or D rings of streptonigrin. We report the identification of the 7-amino-quinoline-5,8-dione core of streptonigrin as a highly potent pharmacophore that acts as a pan-PAD inhibitor.
Recommended Products
| BBF-02642 | Lactonamycin | Inquiry |
| BBF-05862 | Epirubicin | Inquiry |
| BBF-01829 | Deoxynojirimycin | Inquiry |
| BBF-01826 | Deoxymannojirimycin | Inquiry |
| BBF-02614 | Nystatin | Inquiry |
| BBF-01825 | Loganin | Inquiry |
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 ╳
