Anti-malarial activity of N~6-modified purine analogues

Kathleen Too; Daniel M. Brown; Emily Bongard; Vanessa Yardley; Livia Vivas; David Loakes

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Anti-malarial activity of N~6-modified purine analogues

机译：N〜6-修饰的嘌呤类似物的抗疟活性

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Plasmodium falciparum causes one of the deadliest forms of malaria and resistance to the currently available drugs makes it imperative to develop new, safe and potent drugs. Parasites such as P. falciparum are unable to synthesise purines de novo and to this end often have multiple purine uptake and salvage systems. With this in mind, we have designed and synthesised libraries of purine analogues as potential anti-malarial agents. Herein, we report three compounds with promising activity against the highly chloroquine-resistant VS1 P. falciparum namely: N~6-hydroxyadenine (1c), 2-amino-N~6-aminoadenosine (2b) and 2-amino-N~6-amino -N~6-methyladenosine (4b).

机译：恶性疟原虫是疟疾最致命的形式之一，对目前可用的药物产生抗药性使得开发新的，安全的和有效的药物势在必行。诸如恶性疟原虫之类的寄生虫无法从头合成嘌呤，因此通常具有多种嘌呤摄取和挽救系统。考虑到这一点，我们设计并合成了嘌呤类似物作为潜在的抗疟疾药物的文库。在本文中，我们报告了三种具有高度抗氯喹抗性的VS1恶性疟原虫的活性化合物：N〜6-羟基腺嘌呤（1c），2-氨基-N〜6-氨基腺苷（2b）和2-氨基-N〜6 -氨基-N-6-甲基腺苷（4b）。

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来源
《Bioorganic and Medicinal Chemistry》 |2007年第16期|p.5551-5562|共12页
作者
Kathleen Too; Daniel M. Brown; Emily Bongard; Vanessa Yardley; Livia Vivas; David Loakes;
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作者单位

Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK;

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原文格式 PDF
正文语种 eng
中图分类药学;生物化学;
关键词
purine analogues; malaria; tautomerism; nucleosides; plasmodium;

机译：嘌呤类似物;疟疾;互变异构;核苷;疟原虫;

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1. Structure activity relationship, 6-modified purine riboside analogues to activate hSTING, stimulator of interferon genes [J] . Bioorganic and Medicinal Chemistry Letters . 2020,第2期

机译：结构活性关系，6-改良的嘌呤核苷类似物激活HSTING，刺激剂的干扰素基因
2. In vitro anti-malarial activity of N6-modified purine analogs. [J] . Too K, Brown DM, Loakes D, Nucleosides, nucleotides and nucleic acids . 2007,第6a7期

机译：N6-修饰的嘌呤类似物的体外抗疟活性。
3. Altered purine permease activity in a purine-analogue-resistant mutant of Saccharomyces cerevisiae [J] . R A Woods, W R Pickering The biochemical journal . 1972,第3期

机译：啤酒酵母的嘌呤类似物抗性突变体中嘌呤通透酶活性的改变
4. Acyclic nucleoside phosphonates as a new class of anti-malarial compounds: Inhibition of Plasmodium falciparum hypoxanthine-guahine-xanthine phosphoribosyltransferase by 9-2-(2-phosphonoethoxy)ethyl-purines and their branched derivatives [C] . Dana Hockova, Antonin Holy, Dianne T. Keough European Symposium on Organic Chemistry . 2009

机译：环状核苷膦酸盐作为一种新的抗疟疾化合物：抑制疟原虫脱氧黄嘌呤 - 黄嘌呤 - 黄嘌呤磷酰基转移酶的抑制作用9- 2-（2-膦酰基乙氧基）乙基 - 杂物和其支化衍生物
5. Synthesis and antiviral activity of carbocyclic purine analogues. [D] . Ye, Wei. 2004

机译：碳环嘌呤类似物的合成及其抗病毒活性。
6. Altered purine permease activity in a purine-analogue-resistant mutant of Saccharomyces cerevisiae. [O] . W R Pickering, R A Woods 1972

机译：啤酒酵母的嘌呤类似物抗性突变体中嘌呤通透酶活性的改变。
7. Altered purine permease activity in a purine-analogue-resistant mutant of Saccharomyces cerevisiae. [O] . Pickering, W R, Woods, R A 1972

机译：啤酒酵母的嘌呤类似物抗性突变体中嘌呤通透酶活性的改变。

Anti-malarial activity of N~6-modified purine analogues

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