Dideoxyverticillin A: Difference between revisions
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| PIN = (3''S'',3′''S'',5a''R'',5′a''R'',10b''R'',10′b''R'',11a''S'',11′a''S'')-2,2′,3,3′-Tetramethyl-2,2′,3,3′,5a,5′a,6,6′-octahydro-11''H'',11′''H''-[10b,10′b-bi-3,11a-disulfanopyrazino[1′,2′:1,5]pyrrolo[2,3-''b'']indole]-1,1′,4,4′-tetrone |
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| OtherNames = 11, |
| OtherNames = 11,11′-Dideoxyverticillin A; 11,11′-Dideoxyverticillin |
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| CASNo = 12795-76-5 |
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| UNII = BDQ3M208XA |
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| ChEMBL = 2172426 |
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| C=30 | H=28 | N=6 | O=4 | S=4 |
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'''Dideoxyverticillin A''', also known as '''(+)-11,11′-dideoxyverticillin A''', is a complex epipolythiodioxopiperazine<ref>{{Cite journal | title = The epipolythiodioxopiperazine (ETP) class of fungal toxins: distribution, mode of action, functions and biosynthesis |vauthors=Gardiner DM, Waring P, Howlett BJ | journal = Microbiology | date = April 2005 | volume = 151 | issue = 4 | pages = 1021–1032 | doi = 10.1099/mic.0.27847-0 | pmid = 15817772| doi-access = free }}</ref> initially isolated from the [[marine fungus]] ''[[Penicillium]]'' sp. in 1999.<ref>{{cite journal |vauthors=Son BW, Jensen PR, Kauffman CA, Fenical W | title = New cytotoxic epidithiodioxopiperazines related to verticillin A from a marine isolate of the fungus Penicillium | journal = Natural Product Letters | volume = 13 | issue = 3 | pages = 213–222 | date= May 1999 | doi = 10.1080/10575639908048788 }}</ref> It has also been found in the marine fungus ''[[Bionectriaceae]]'',<ref name="pmid22968289">{{cite journal |vauthors=Figueroa M, Graf TN, Ayers S, Adcock AF, Kroll DJ, Yang J, Swanson SM, Munoz-Acuna U, de Blanco EJ, Agrawal R, Wani MC | title = Cytotoxic epipolythiodioxopiperazine alkaloids from filamentous fungi of the Bionectriaceae | journal = The Journal of Antibiotics | volume = 65 | issue = 11 | pages = 559–564 | date= November 2012 | pmid = 22968289| doi = 10.1038/ja.2012.69 | pmc=3573876}}</ref> and belongs to a class of naturally occurring [[2,5-Diketopiperazine|2,5-diketopiperazines]].<ref name="pmid22575049">{{Cite journal | title = 2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products | author = Borthwick AD | journal = Chemical Reviews | date = May 2012 | volume = 112 | issue = 7 | pages = 3641–3716 | doi = 10.1021/cr200398y | pmid = 22575049}}</ref> |
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Dideoxyverticillin A (11,11’-dideoxyverticillin A) is a complex epipolythiodioxo-[[piperazine]] isolated from a marine fungus. Dideoxyverticillin A's reported anticancer mechanism is that it acts as a [[farnesyl transferase inhibitor]]. Dozens of semi-synthetic anticancer compounds have been made from Dideoxyverticillin A. [[Dimer (chemistry)|Dimeric]] derivatives are reported to have better anticancer activity. |
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Dideoxyverticillin A potently inhibits the [[tyrosine kinase]] activity of the [[epidermal growth factor receptor]] (median inhibitory concentration = 0.14 nM), exhibits antiangiogenic activity, and has efficacy against several cancer cell lines.<ref name="pmid22575049" /> Its reported anticancer mechanism is that it acts as a [[farnesyl transferase inhibitor]]. Dozens of semi-synthetic anticancer compounds have been made from dideoxyverticillin A. Dimeric derivatives are reported to have better anticancer activity.<ref name="pmid23914293">{{cite journal |vauthors=Boyer N, Morrison KC, Kim J, Hergenrother PJ, Movassaghi M | title = Synthesis and anticancer activity of epipolythiodiketopiperazine alkaloids | journal = Chemical Science | volume = 4 | issue = 4 | pages = 1646–1657 | date= 2013 | pmid = 23914293 | doi = 10.1039/C3SC50174D | pmc=3728915| url= http://dspace.mit.edu/bitstream/1721.1/95495/1/Movassaghi_Synthesis%20and.pdf }}</ref> |
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The [[enantioselective]] first total synthesis of (+)-11,11′-dideoxyverticillin A, the structure of which contains many sterically congested, [[wikt:contiguity|contiguous]] stereogenic centers as well as acid- and base-labile and [[redox]]-sensitive functionality, was biosynthetically inspired and achieved with high levels of chemical sophistication.<ref name="pmid19359584">{{cite journal |vauthors=Kim J, Ashenhurst JA, Movassaghi M | title = Total synthesis of (+)-11,11'-dideoxyverticillin A | journal = Science | volume = 324 | issue = 5924 | pages = 238–241 | date= April 2009 | pmid = 19359584 | doi = 10.1126/science.1170777 | pmc=4238916}}</ref> |
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==References== |
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{{Reflist}} |
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==External links== |
==External links== |
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*[http://web.mit.edu/newsoffice/2013/chemists-find-help-from-nature-in-fighting-cancer-0227.html MIT News - 11, |
*[http://web.mit.edu/newsoffice/2013/chemists-find-help-from-nature-in-fighting-cancer-0227.html MIT News - 11,11′-Dideoxyverticillin] |
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*{{cite journal |vauthors=Shi Y, Zhang Y, Ni Y, Shi G, Yang H |title=11-脱氧轮枝菌素A引起前列腺癌PC3M细胞Caspase依赖的凋亡 |trans-title=11'-Deoxyverticillin A induces caspase-dependent cell apoptosis in PC3M cells |language=zh |journal=Sheng Wu Gong Cheng Xue Bao |volume=28 |issue=1 |pages=96–103 |date=January 2012 |pmid=22667113 |url=http://d.wanfangdata.com.cn/Periodical_swgcxb201201011.aspx}} |
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*[http://www.ncbi.nlm.nih.gov/pubmed/22667113 11'-Deoxyverticillin A induces caspase-dependent cell apoptosis in PC3M cells] |
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*[http://www.ncbi.nlm.nih.gov/pubmed/22968289 Cytotoxic epipolythiodioxopiperazine alkaloids from filamentous fungi of the Bionectriaceae] |
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[[Category:Farnesyltransferase inhibitors]] |
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{{organic-chem-stub}} |
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[[Category:Bionectriaceae]] |
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[[Category:Diketopiperazines]] |
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Latest revision as of 01:14, 13 August 2023
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| Names | |
|---|---|
| Preferred IUPAC name
(3S,3′S,5aR,5′aR,10bR,10′bR,11aS,11′aS)-2,2′,3,3′-Tetramethyl-2,2′,3,3′,5a,5′a,6,6′-octahydro-11H,11′H-[10b,10′b-bi-3,11a-disulfanopyrazino[1′,2′:1,5]pyrrolo[2,3-b]indole]-1,1′,4,4′-tetrone | |
| Other names
11,11′-Dideoxyverticillin A; 11,11′-Dideoxyverticillin
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| Identifiers | |
| ChEMBL | |
| ChemSpider | |
PubChem CID
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| UNII | |
| Properties | |
| C30H28N6O4S4 | |
| Molar mass | 664.83 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Dideoxyverticillin A, also known as (+)-11,11′-dideoxyverticillin A, is a complex epipolythiodioxopiperazine[1] initially isolated from the marine fungus Penicillium sp. in 1999.[2] It has also been found in the marine fungus Bionectriaceae,[3] and belongs to a class of naturally occurring 2,5-diketopiperazines.[4]
Dideoxyverticillin A potently inhibits the tyrosine kinase activity of the epidermal growth factor receptor (median inhibitory concentration = 0.14 nM), exhibits antiangiogenic activity, and has efficacy against several cancer cell lines.[4] Its reported anticancer mechanism is that it acts as a farnesyl transferase inhibitor. Dozens of semi-synthetic anticancer compounds have been made from dideoxyverticillin A. Dimeric derivatives are reported to have better anticancer activity.[5]
The enantioselective first total synthesis of (+)-11,11′-dideoxyverticillin A, the structure of which contains many sterically congested, contiguous stereogenic centers as well as acid- and base-labile and redox-sensitive functionality, was biosynthetically inspired and achieved with high levels of chemical sophistication.[6]
References
[edit]- ^ Gardiner DM, Waring P, Howlett BJ (April 2005). "The epipolythiodioxopiperazine (ETP) class of fungal toxins: distribution, mode of action, functions and biosynthesis". Microbiology. 151 (4): 1021–1032. doi:10.1099/mic.0.27847-0. PMID 15817772.
- ^ Son BW, Jensen PR, Kauffman CA, Fenical W (May 1999). "New cytotoxic epidithiodioxopiperazines related to verticillin A from a marine isolate of the fungus Penicillium". Natural Product Letters. 13 (3): 213–222. doi:10.1080/10575639908048788.
- ^ Figueroa M, Graf TN, Ayers S, Adcock AF, Kroll DJ, Yang J, Swanson SM, Munoz-Acuna U, de Blanco EJ, Agrawal R, Wani MC (November 2012). "Cytotoxic epipolythiodioxopiperazine alkaloids from filamentous fungi of the Bionectriaceae". The Journal of Antibiotics. 65 (11): 559–564. doi:10.1038/ja.2012.69. PMC 3573876. PMID 22968289.
- ^ a b Borthwick AD (May 2012). "2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products". Chemical Reviews. 112 (7): 3641–3716. doi:10.1021/cr200398y. PMID 22575049.
- ^ Boyer N, Morrison KC, Kim J, Hergenrother PJ, Movassaghi M (2013). "Synthesis and anticancer activity of epipolythiodiketopiperazine alkaloids" (PDF). Chemical Science. 4 (4): 1646–1657. doi:10.1039/C3SC50174D. PMC 3728915. PMID 23914293.
- ^ Kim J, Ashenhurst JA, Movassaghi M (April 2009). "Total synthesis of (+)-11,11'-dideoxyverticillin A". Science. 324 (5924): 238–241. doi:10.1126/science.1170777. PMC 4238916. PMID 19359584.
External links
[edit]- MIT News - 11,11′-Dideoxyverticillin
- Shi Y, Zhang Y, Ni Y, Shi G, Yang H (January 2012). "11-脱氧轮枝菌素A引起前列腺癌PC3M细胞Caspase依赖的凋亡" [11'-Deoxyverticillin A induces caspase-dependent cell apoptosis in PC3M cells]. Sheng Wu Gong Cheng Xue Bao (in Chinese). 28 (1): 96–103. PMID 22667113.
