Siomycin A
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| Category | Antibiotics |
| Catalog number | BBF-04577 |
| CAS | 12656-09-6 |
| Molecular Weight | 1648.84 |
| Molecular Formula | C71H81N19O18S5 |
| Purity | >95% by HPLC |
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Description
A macrocyclic antibiotic first isolated from S. sioyaensis with potent and selective antibacterial activity. It is a potent inhibitor of the oncogenic transcription factor, foxm1. It inhibits foxm1-induced cell growth on soft agar and selectively kills transformed but not normal cells in vitro.
Specification
| Synonyms | Mutabilycin; Sporangiomycin; 6741-21; NSC 285116; Antibiotic 6741-21; (1-L-valine)-[2-(2,3-didehydro-alanine)]-thiostrepton; Thiostrepton, 1-Valine-2-(2,3-didehydroalanine)- |
| Storage | Store at -20°C |
| IUPAC Name | N-[3-[(3-amino-3-oxoprop-1-en-2-yl)amino]-3-oxoprop-1-en-2-yl]-2-[(1R,8S,11Z,15S,18S,25S,26R,35R,37S,46S,53S,59S)-18-[(2S,3R)-2,3-dihydroxybutan-2-yl]-11-ethylidene-59-hydroxy-8-[(1R)-1-hydroxyethyl]-31-[(1S)-1-hydroxyethyl]-26,46-dimethyl-40,43-dimethylidene-6,9,16,23,28,38,41,44,47-nonaoxo-37-propan-2-yl-27-oxa-3,13,20,56-tetrathia-7,10,17,24,36,39,42,45,48,52,58,61,62,63,64-pentadecazanonacyclo[23.23.9.329,35.12,5.112,15.119,22.154,57.01,53.032,60]tetrahexaconta-2(64),4,12(63),19(62),21,29(61),30,32(60),33,51,54,57-dodecaen-51-yl]-1,3-thiazole-4-carboxamide |
| Canonical SMILES | CC=C1C2=NC(CS2)C(=O)NC(C3=NC(=CS3)C(=O)NC4C(OC(=O)C5=NC6=C(C=CC(C6O)NC(C(=O)NC(=C)C(=O)NC(=C)C(=O)NC(C(=O)NC7(CCC(=NC7C8=CSC4=N8)C9=NC(=CS9)C(=O)NC(=C)C(=O)NC(=C)C(=O)N)C2=NC(=CS2)C(=O)NC(C(=O)N1)C(C)O)C)C(C)C)C(=C5)C(C)O)C)C(C)(C(C)O)O |
| InChI | InChI=1S/C71H81N19O18S5/c1-14-37-64-83-44(22-109-64)61(103)89-52(70(13,107)34(12)93)67-85-43(23-112-67)59(101)88-48-33(11)108-68(106)40-19-36(31(9)91)35-15-16-38(50(94)49(35)79-40)78-46(25(2)3)62(104)77-29(7)56(98)74-27(5)55(97)75-30(8)57(99)90-71(69-86-45(24-113-69)60(102)87-47(32(10)92)63(105)81-37)18-17-39(80-51(71)41-20-111-66(48)82-41)65-84-42(21-110-65)58(100)76-28(6)54(96)73-26(4)53(72)95/h14-16,19-21,23-25,30-34,38,44,46-48,50-52,78,91-94,107H,4-7,17-18,22H2,1-3,8-13H3,(H2,72,95)(H,73,96)(H,74,98)(H,75,97)(H,76,100)(H,77,104)(H,81,105)(H,87,102)(H,88,101)(H,89,103)(H,90,99)/b37-14-/t30-,31-,32+,33+,34+,38+,44+,46-,47-,48-,50-,51+,52+,70+,71+/m0/s1 |
| InChI Key | AKFVOKPQHFBYCA-KJULAZMPSA-N |
| Source | Streptomyces sp. |
Properties
| Appearance | White Solid |
| Antibiotic Activity Spectrum | Bacteria |
| Density | 1.65±0.1 g/cm3 (Predicted) |
| Solubility | Soluble in DMF, DMSO; Moderately soluble in Methanol, Ethanol; Poorly soluble in Water |
Reference Reading
1. Siomycin A targets brain tumor stem cells partially through a MELK-mediated pathway
Eric Wexler, Bin Hu, Diana Lam, Mariano Viapiano, Koppany Visnyei, Dan R Laks, Paul S Mischel, Ichiro Nakano, Kuniyasu Saigusa, Kaushal Joshi, Yuko Nakamura, Momoko Watanabe, Harley I Kornblum Neuro Oncol . 2011 Jun;13(6):622-34. doi: 10.1093/neuonc/nor023.
Glioblastoma multiforme (GBM) is a devastating disease, and the current therapies have only palliative effect. Evidence is mounting to indicate that brain tumor stem cells (BTSCs) are a minority of tumor cells that are responsible for cancer initiation, propagation, and maintenance. Therapies that fail to eradicate BTSCs may ultimately lead to regrowth of residual BTSCs. However, BTSCs are relatively resistant to the current treatments. Development of novel therapeutic strategies that effectively eradicate BTSC are, therefore, essential. In a previous study, we used patient-derived GBM sphere cells (stemlike GBM cells) to enrich for BTSC and identified maternal embryonic leucine-zipper kinase (MELK) as a key regulator of survival of stemlike GBM cells in vitro. Here, we demonstrate that a thiazole antibiotic, siomycin A, potently reduced MELK expression and inhibited tumor growth in vivo. Treatment of stemlike GBM cells with siomycin A resulted in arrested self-renewal, decreased invasion, and induced apoptosis but had little effect on growth of the nonstem cells of matched tumors or normal neural stem/progenitor cells. MELK overexpression partially rescued the phenotype of siomycin A-treated stemlike GBM cells. In vivo, siomycin A pretreatment abraded the sizes of stemlike GBM cell-derived tumors in immunodeficient mice. Treatment with siomycin A of mice harboring intracranial tumors significantly prolonged their survival period compared with the control mice. Together, this study may be the first model to partially target stemlike GBM cells through a MELK-mediated pathway with siomycin A to pave the way for effective treatment of GBM.
2. Total synthesis of siomycin A: construction of synthetic segments
Taiji Goto, Mitsunori Kohno, Kazuyuki Shinko, Masaya Nakata, Kimiko Hashimoto, Shuhei Higashibayashi, Kengo Suzuki, Yukiko Satouchi, Shunya Suzuki, Hiraku Tohmiya, Tomonori Mori Chem Asian J . 2008 Jun 2;3(6):984-1012. doi: 10.1002/asia.200800032.
The five practical segments for the total synthesis of siomycin A, that is, the dehydropiperidine segment A (5), the pentapeptide segment B (3), the dihydroquinoline segment C (6), and the beta-phenylselenoalanine dipeptide segments D (7) and E (4), were synthesized. Segment A (5) was constructed by the coupling of the azomethine ylide and the chiral sulfinimine, followed by the stereoselective reduction of the six-membered imine function. Segment B (3) was synthesized by the phenylselenylation of the beta-lactone, stereoselective vinylzinc addition to the chiral sulfinimine, and oxazoline-thioamide conversion. Segment C (6) was prepared by the one-pot olefination of the tetrahydroquinoline N-oxide using triflic anhydride and triethylamine, stereoselective reduction of the methyl ketone function, and regioselective Yb(OTf)(3)-catalyzed epoxide opening by the amino group. Segments D (7) and E (4) were synthesized by coupling of the properly protected beta-phenylselenoalanines.
3. Effects and mechanism of siomycin A on the growth and apoptosis of MiaPaCa-2 cancer cells
Hao-Yi Meng, Li-Jie Yuan, Wei Wang, Bin Wang, Jing Chen Oncol Lett . 2019 Sep;18(3):2869-2876. doi: 10.3892/ol.2019.10633.
Siomycin A is a type of thiopeptide antibiotic that is isolated from the fermentation products of an endophytic actinomycin, which is derived from the medicinal plantAcanthopanax senticosus. The present study investigated whether siomycin A has antitumor effectsin vitroon a variety of cell lines. A Cell Counting Kit-8 assay was performed to detect the effects of siomycin A on cell viability; morphological changes in the MiaPaCa-2 cell line were analyzed using an inverted phase contrast microscope. A Transwell migration assay was applied to detect cell migration ability. The cytoskeleton was observed by laser confocal microscopy, and apoptosis was detected using flow cytometry. A western blot assay was used to detect the expression of matrix metalloproteinase (MMP)-2, MMP-9 and α-tubulin. The results revealed that siomycin A inhibited the proliferation of human tumor cell lines of different origins. As the concentration of siomycin A increased, the cell density decreased gradually and cells exhibited a morphological change from spindle to spherical shape. Furthermore, 24 h after administration, the cell migration ability was inhibited. The cytoskeleton complexity and morphological changes were increased after administration of siomycin A. The percentage of apoptotic cells was significantly increased and the expression levels of MMP-2, MMP-9 and α-tubulin were downregulated by siomycin A. Therefore, siomycin A was determined to effectively inhibit the proliferative ability of a variety of human tumor cell lines. Siomycin A was also determined to affect the cytoskeleton of tumor cells by downregulating the expression of α-tubulin protein.
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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 ╳
