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酰基富烯,一类新型强效抗肿瘤药物。

Acylfulvenes, a new class of potent antitumor agents.

作者信息

McMorris T C, Kelner M J, Wang W, Diaz M A, Estes L A, Taetle R

机构信息

Department of Chemistry, University of California, San Diego, La Jolla 92093-0506, USA.

出版信息

Experientia. 1996 Jan 16;52(1):75-80. doi: 10.1007/BF01922420.

DOI:10.1007/BF01922420
PMID:8575564
Abstract

Acylfulvene, derived from the sesquiterpene illudin S by treatment with acid (reverse Prins reaction), is far less reactive to thiols than illudin S. However, it is reduced readily to an aromatic product, in the same way as illudin S. This may explain its greatly improved therapeutic index compared to that of the parent compound.

摘要

酰基富烯是通过用酸处理倍半萜伊利菌素S(逆普林斯反应)得到的,它与硫醇的反应活性比伊利菌素S低得多。然而,它与伊利菌素S一样,很容易被还原为芳香产物。这可能解释了它与母体化合物相比,治疗指数有了很大提高。

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1
Acylfulvenes, a new class of potent antitumor agents.酰基富烯,一类新型强效抗肿瘤药物。
Experientia. 1996 Jan 16;52(1):75-80. doi: 10.1007/BF01922420.
2
Metabolism of antitumor acylfulvene by rat liver cytosol.大鼠肝细胞溶质对抗肿瘤酰基富烯的代谢
Biochem Pharmacol. 1999 Jan 1;57(1):83-8. doi: 10.1016/s0006-2952(98)00273-1.
3
(Hydroxymethyl)acylfulvene: an illudin derivative with superior antitumor properties.
J Nat Prod. 1996 Sep;59(9):896-9. doi: 10.1021/np960450y.
4
Sulfotransferase-independent genotoxicity of illudin S and its acylfulvene derivatives in bacterial and mammalian cells.磺基转移酶非依赖性的硫代长春碱 S 和其酰基呋喃衍生物在细菌和哺乳动物细胞中的遗传毒性。
Arch Toxicol. 2014 Jan;88(1):161-9. doi: 10.1007/s00204-013-1097-2. Epub 2013 Jul 24.
5
Quantification of acylfulvene- and illudin S-DNA adducts in cells with variable bioactivation capacities.定量检测具有不同生物活化能力的细胞中的酰基富烯和鹅膏蕈碱 S-DNA 加合物。
Chem Res Toxicol. 2013 Jan 18;26(1):146-55. doi: 10.1021/tx300430r. Epub 2012 Dec 19.
6
Chemical and enzymatic reductive activation of acylfulvene to isomeric cytotoxic reactive intermediates.酰基富烯的化学和酶促还原活化生成具有立体异构体的细胞毒性反应性中间产物。
Chem Res Toxicol. 2011 Nov 21;24(11):2044-54. doi: 10.1021/tx200401u. Epub 2011 Oct 14.
7
Metabolism of antitumor hydroxymethylacylfulvene by rat liver cytosol.
Drug Metab Dispos. 1999 Sep;27(9):983-5.
8
Chemistry and biology of acylfulvenes: sesquiterpene-derived antitumor agents.酰基富烯的化学与生物学:倍半萜衍生的抗肿瘤药物
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Efficacy of Acylfulvene Illudin analogues against a metastatic lung carcinoma MV522 xenograft nonresponsive to traditional anticancer agents: retention of activity against various mdr phenotypes and unusual cytotoxicity against ERCC2 and ERCC3 DNA helicase-deficient cells.
Cancer Res. 1995 Nov 1;55(21):4936-40.
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Enhancement of the antitumor effect of illudin S by including it into liposomes.通过将伊鲁丁S包封于脂质体中来增强其抗肿瘤作用。
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本文引用的文献

1
FUNGAL METABOLITES. THE STRUCTURES OF THE NOVEL SESQUITERPENOIDS ILLUDIN-S AND -M.真菌代谢产物。新型倍半萜伊利丁-S和-M的结构。
J Am Chem Soc. 1965 Apr 5;87:1594-600. doi: 10.1021/ja01085a031.
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Efficacy of Acylfulvene Illudin analogues against a metastatic lung carcinoma MV522 xenograft nonresponsive to traditional anticancer agents: retention of activity against various mdr phenotypes and unusual cytotoxicity against ERCC2 and ERCC3 DNA helicase-deficient cells.
Cancer Res. 1995 Nov 1;55(21):4936-40.
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Illudin S (lampterol).鬼笔环肽 S(亮菌甲素)。
在温和条件下,通过使用2,3-二氧代-4-亚苄基吡咯烷的形式[2 + 1]环加成反应实现螺环丙烷的非对映选择性合成。
Molecules. 2017 Feb 22;22(2):328. doi: 10.3390/molecules22020328.
4
Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions.共价修饰剂:从化学角度看α,β-不饱和羰基化合物与硫醇通过杂迈克尔加成反应的反应活性
J Med Chem. 2017 Feb 9;60(3):839-885. doi: 10.1021/acs.jmedchem.6b00788. Epub 2016 Dec 20.
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Improved efficacy of acylfulvene in colon cancer cells when combined with a nuclear excision repair inhibitor.酰基富烯与核切除修复抑制剂联合使用时可提高结肠癌细胞的疗效。
Chem Res Toxicol. 2013 Nov 18;26(11):1674-82. doi: 10.1021/tx400255f. Epub 2013 Nov 5.
6
Quantification of acylfulvene- and illudin S-DNA adducts in cells with variable bioactivation capacities.定量检测具有不同生物活化能力的细胞中的酰基富烯和鹅膏蕈碱 S-DNA 加合物。
Chem Res Toxicol. 2013 Jan 18;26(1):146-55. doi: 10.1021/tx300430r. Epub 2012 Dec 19.
7
Chemical and enzymatic reductive activation of acylfulvene to isomeric cytotoxic reactive intermediates.酰基富烯的化学和酶促还原活化生成具有立体异构体的细胞毒性反应性中间产物。
Chem Res Toxicol. 2011 Nov 21;24(11):2044-54. doi: 10.1021/tx200401u. Epub 2011 Oct 14.
8
Susceptibility of the antioxidant selenoenyzmes thioredoxin reductase and glutathione peroxidase to alkylation-mediated inhibition by anticancer acylfulvenes.抗氧化酶硒代酶硫氧还蛋白还原酶和谷胱甘肽过氧化物酶对抗癌酰基富烯介导的烷基化抑制作用的敏感性。
Chem Res Toxicol. 2011 May 16;24(5):726-36. doi: 10.1021/tx2000152. Epub 2011 Apr 12.
9
Profiling patterns of glutathione reductase inhibition by the natural product illudin S and its acylfulvene analogues.天然产物伊鲁丁S及其酰基富烯类似物对谷胱甘肽还原酶抑制作用的分析模式
Mol Biosyst. 2009 Sep;5(9):1013-24. doi: 10.1039/b904720d. Epub 2009 Jul 8.
10
A phase II trial of 6-hydroxymethylacylfulvene (MGI-114, irofulven) in patients with advanced non-small cell cancer previously treated with chemotherapy.一项针对先前接受过化疗的晚期非小细胞癌患者的6-羟甲基酰基富烯(MGI-114,irofulven)II期试验。
Invest New Drugs. 2001;19(1):85-8. doi: 10.1023/a:1006433528750.
Tetrahedron. 1965 May;21(5):1231-46. doi: 10.1016/0040-4020(65)80065-5.
4
Structure of lampterol (illudin S).灯台毒素(隐杯伞素S)的结构。
Tetrahedron. 1965 Sep;21(9):2671-6. doi: 10.1016/s0040-4020(01)93922-5.
5
Preclinical evaluation of illudins as anticancer agents.
Cancer Res. 1987 Jun 15;47(12):3186-9.
6
Poisoning with the North American Jack O'Lantern mushroom, Omphalotus illudens.北美橙盖鹅膏菌(Omphalotus illudens)中毒
J Toxicol Clin Toxicol. 1988;26(1-2):81-8. doi: 10.3109/15563658808995399.
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Preclinical evaluation of illudins as anticancer agents: basis for selective cytotoxicity.
J Natl Cancer Inst. 1990 Oct 3;82(19):1562-5. doi: 10.1093/jnci/82.19.1562.
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Cloned low metastatic variants from human lung carcinoma metastases.
Anticancer Res. 1990 May-Jun;10(3):637-43.
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On the mechanism of toxicity of illudins: the role of glutathione.
Chem Res Toxicol. 1990 Nov-Dec;3(6):574-9. doi: 10.1021/tx00018a013.
10
Metabolism by rat liver cytosol of illudin S, a toxic substance of Lampteromyces japonicus. II. Characterization of illudin S-metabolizing enzyme.日本亮耳菌的有毒物质鬼笔素 S 在大鼠肝细胞溶质中的代谢。II. 鬼笔素 S 代谢酶的特性
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