Simocyclinone D8
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| Category | Antibiotics |
| Catalog number | BBF-02914 |
| CAS | 301845-97-6 |
| Molecular Weight | 932.27 |
| Molecular Formula | C46H42ClNO18 |
| Purity | ≥95% |
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Description
It is produced by the strain of Streptomyces antibioticus Tu 6040. It has moderate anti-gram-positive bacteria activity and has inhibitory effect on a variety of tumor cells. It inhibits HMO2, MCF7 and HEP G2 cells with GI50 (μmol/L) of 0.50, 0.95 and >50, respectively.
Specification
| Synonyms | 9-[4-O-Acetyl-3-O-[10-[(8-chloro-4,7-dihydroxy-2-oxo-2H-1-benzopyran-3-yl)amino]-1,10-dioxo-2,4,6,8-decatetraenyl]-2,6-dideoxy-beta-D-arabino-hexopyranosyl]-4a,5,6,12b-tetrahydro-4a,6,7,8,12b-pentahydroxy-3-methyl-6a,12a-epoxybenz[a]anthracene-1,12(4H,7H)-dione; (1R)-4-O-acetyl-1,5-anhydro-3-O-{(2E,4E,6E,8E)-10-[(8-chloro-4,7-dihydroxy-2-oxo-2H-chromen-3-yl)amino]-10-oxodeca-2,4,6,8-tetraenoyl}-2,6-dideoxy-1-[(4aR,6S,6aS,7S,12aS,12bR)-4a,6,7,8,12b-pentahydroxy-3-methyl-1,12-dioxo-1,4,4a,5,6,7,12,12b-octahydro-6a,12a-epoxytetraphen-9-yl]-D-arabino-hexitol |
| IUPAC Name | [(2R,3R,4R,6R)-3-acetyloxy-2-methyl-6-[(1S,2R,7R,9S,10S,11S)-2,7,9,11,13-pentahydroxy-5-methyl-3,18-dioxo-19-oxapentacyclo[8.8.1.01,10.02,7.012,17]nonadeca-4,12(17),13,15-tetraen-14-yl]oxan-4-yl] (2E,4E,6E,8E)-10-[(8-chloro-4,7-dihydroxy-2-oxochromen-3-yl)amino]-10-oxodeca-2,4,6,8-tetraenoate |
| Canonical SMILES | CC1C(C(CC(O1)C2=C(C3=C(C=C2)C(=O)C45C(C3O)(O4)C(CC6(C5(C(=O)C=C(C6)C)O)O)O)O)OC(=O)C=CC=CC=CC=CC(=O)NC7=C(C8=C(C(=C(C=C8)O)Cl)OC7=O)O)OC(=O)C |
| InChI | InChI=1S/C46H42ClNO18/c1-20-16-29(51)45(61)43(60,18-20)19-30(52)44-41(58)33-24(40(57)46(44,45)66-44)13-12-23(36(33)55)27-17-28(38(21(2)62-27)63-22(3)49)64-32(54)11-9-7-5-4-6-8-10-31(53)48-35-37(56)25-14-15-26(50)34(47)39(25)65-42(35)59/h4-16,21,27-28,30,38,41,50,52,55-56,58,60-61H,17-19H2,1-3H3,(H,48,53)/b6-4+,7-5+,10-8+,11-9+/t21-,27-,28-,30+,38-,41+,43-,44+,45-,46-/m1/s1 |
| InChI Key | PLEGMCYXNQPJNV-VHSVXIAXSA-N |
Properties
| Appearance | Yellow Powder |
| Antibiotic Activity Spectrum | Gram-positive bacteria; Neoplastics (Tumor) |
| Boiling Point | 1161.9±65.0°C (Predicted) |
| Melting Point | >200°C |
| Density | 1.67±0.1 g/cm3 (Predicted) |
| Solubility | Soluble in Methanol |
Reference Reading
1. Flavone-based analogues inspired by the natural product simocyclinone D8 as DNA gyrase inhibitors
Jenson Verghese, Thuy Nguyen, Lisa M Oppegard, Lauren M Seivert, Hiroshi Hiasa, Keith C Ellis Bioorg Med Chem Lett. 2013 Nov 1;23(21):5874-7. doi: 10.1016/j.bmcl.2013.08.094. Epub 2013 Sep 5.
The increasing occurrence of drug-resistant bacterial infections in the clinic has created a need for new antibacterial agents. Natural products have historically been a rich source of both antibiotics and lead compounds for new antibacterial agents. The natural product simocyclinone D8 (SD8) has been reported to inhibit DNA gyrase, a validated antibacterial drug target, by a unique catalytic inhibition mechanism of action. In this work, we have prepared simplified flavone-based analogues inspired by the complex natural product and evaluated their inhibitory activity and mechanism of action. While two of these compounds do inhibit DNA gyrase, they do so by a different mechanism of action than SD8, namely DNA intercalation.
2. SimReg1 is a master switch for biosynthesis and export of simocyclinone D8 and its precursors
Liliya Horbal, Yuriy Rebets, Mariya Rabyk, Roman Makitrynskyy, Andriy Luzhetskyy, Victor Fedorenko, Andreas Bechthold AMB Express. 2012 Jan 3;2(1):1. doi: 10.1186/2191-0855-2-1.
Analysis of the simocyclinone biosynthesis (sim) gene cluster of Streptomyces antibioticus Tü6040 led to the identification of a putative pathway specific regulatory gene simReg1. In silico analysis places the SimReg1 protein in the OmpR-PhoB subfamily of response regulators. Gene replacement of simReg1 from the S. antibioticus chromosome completely abolishes simocyclinone production indicating that SimReg1 is a key regulator of simocyclinone biosynthesis. Results of the DNA-shift assays and reporter gene expression analysis are consistent with the idea that SimReg1 activates transcription of simocyclinone biosynthesis, transporter genes, regulatory gene simReg3 and his own transcription. The presence of extracts (simocyclinone) from S. antibioticus Tü6040 × pSSimR1-1 could dissociate SimReg1 from promoter regions. A preliminary model for regulation of simocyclinone biosynthesis and export is discussed.
3. A new crystal structure of the bifunctional antibiotic simocyclinone D8 bound to DNA gyrase gives fresh insight into the mechanism of inhibition
Stephen J Hearnshaw, Marcus J Edwards, Clare E Stevenson, David M Lawson, Anthony Maxwell J Mol Biol. 2014 May 15;426(10):2023-33. doi: 10.1016/j.jmb.2014.02.017. Epub 2014 Mar 1.
Simocyclinone D8 (SD8) is an antibiotic produced by Streptomyces antibioticus that targets DNA gyrase. A previous structure of SD8 complexed with the N-terminal domain of the DNA gyrase A protein (GyrA) suggested that four SD8 molecules stabilized a tetramer of the protein; subsequent mass spectrometry experiments suggested that a protein dimer with two symmetry-related SD8s was more likely. This work describes the structures of a further truncated form of the GyrA N-terminal domain fragment with and without SD8 bound. The structure with SD8 has the two SD8 molecules bound within the same GyrA dimer. This new structure is entirely consistent with the mutations in GyrA that confer SD8 resistance and, by comparison with a new apo structure of the GyrA N-terminal domain, reveals the likely conformation changes that occur upon SD8 binding and the detailed mechanism of SD8 inhibition of gyrase. Isothermal titration calorimetry experiments are consistent with the crystallography results and further suggest that a previously observed complex between SD8 and GyrB is ~1000-fold weaker than the interaction with GyrA.
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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 ╳
