2-氧代-四氢-1,8-萘啶作为疟疾蛋白法尼基转移酶的选择性抑制剂及抗疟药物。
2-Oxo-tetrahydro-1,8-naphthyridines as selective inhibitors of malarial protein farnesyltransferase and as anti-malarials.
作者信息
Olepu Srinivas, Suryadevara Praveen Kumar, Rivas Kasey, Yokoyama Kohei, Verlinde Christophe L M J, Chakrabarti Debopam, Van Voorhis Wesley C, Gelb Michael H
机构信息
Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
出版信息
Bioorg Med Chem Lett. 2008 Jan 15;18(2):494-7. doi: 10.1016/j.bmcl.2007.11.104. Epub 2007 Dec 3.
Abstract
A new class of 2-oxo-tetrahydro-1,8-naphthyridine-based protein farnesyltransferase inhibitors were synthesized and found to inhibit protein farnesyltransferase from the malaria parasite with potencies in the low nanomolar range. The compounds were much less potent on mammalian protein prenyltransferases. Two of the compounds block the growth of malaria in culture with potencies in the sub-micromolar range. Some of the compounds were found to be much more metabolically stable than previously described tetrahydroquinoline-based protein farnesyltransferase inhibitors.
摘要
合成了一类新型的基于2-氧代-四氢-1,8-萘啶的蛋白质法尼基转移酶抑制剂，发现它们能抑制疟原虫的蛋白质法尼基转移酶，效力在低纳摩尔范围内。这些化合物对哺乳动物蛋白质异戊二烯基转移酶的效力要低得多。其中两种化合物在亚微摩尔范围内能阻断培养物中疟原虫的生长。发现一些化合物的代谢稳定性比先前描述的基于四氢喹啉的蛋白质法尼基转移酶抑制剂高得多。
相似文献
1
2-Oxo-tetrahydro-1,8-naphthyridines as selective inhibitors of malarial protein farnesyltransferase and as anti-malarials.2-氧代-四氢-1,8-萘啶作为疟疾蛋白法尼基转移酶的选择性抑制剂及抗疟药物。
Bioorg Med Chem Lett. 2008 Jan 15;18(2):494-7. doi: 10.1016/j.bmcl.2007.11.104. Epub 2007 Dec 3.
2
A Review on Plasmodium falciparum-Protein Farnesyltransferase Inhibitors as Antimalarial Drug Targets.疟原虫法尼基蛋白转移酶抑制剂作为抗疟药物靶点的研究进展。
Curr Drug Targets. 2017;18(14):1676-1686. doi: 10.2174/1389450117666160823165004.
3
Peptidomimetic inhibitors of protein farnesyltransferase show potent antimalarial activity.蛋白质法尼基转移酶的拟肽抑制剂具有强大的抗疟活性。
Bioorg Med Chem Lett. 2001 Mar 26;11(6):761-4. doi: 10.1016/s0960-894x(01)00055-5.
4
Identification, Characterization, and Optimization of 2,8-Disubstituted-1,5-naphthyridines as Novel Plasmodium falciparum Phosphatidylinositol-4-kinase Inhibitors with in Vivo Efficacy in a Humanized Mouse Model of Malaria.鉴定、表征和优化 2,8-二取代-1,5-萘啶作为新型恶性疟原虫磷脂酰肌醇-4-激酶抑制剂，在疟疾人源化小鼠模型中具有体内疗效。
J Med Chem. 2018 Jul 12;61(13):5692-5703. doi: 10.1021/acs.jmedchem.8b00648. Epub 2018 Jun 27.
5
Novel lead structures for antimalarial farnesyltransferase inhibitors.抗疟法尼基转移酶抑制剂的新型先导结构。
Pharmazie. 2005 May;60(5):323-7. doi: 10.1002/chin.200536090.
6
2-Oxotetrahydroquinoline-based antimalarials with high potency and metabolic stability.具有高效力和代谢稳定性的基于2-氧代四氢喹啉的抗疟药。
J Med Chem. 2008 Feb 14;51(3):384-7. doi: 10.1021/jm7013138. Epub 2008 Jan 17.
7
Protein farnesyltransferase inhibitors exhibit potent antimalarial activity.蛋白质法尼基转移酶抑制剂具有强大的抗疟活性。
J Med Chem. 2005 Jun 2;48(11):3704-13. doi: 10.1021/jm0491039.
8
Inhibitors of farnesyltransferase: 5-arylacryloylaminobenzophenones show antimalarial activity.法尼基转移酶抑制剂：5-芳基丙烯酰氨基二苯甲酮具有抗疟活性。
Pharmazie. 2003 Apr;58(4):289-90.
9
Novel N-(4-Piperidinyl)benzamide antimalarials with mammalian protein farnesyltransferase inhibitory activity.具有哺乳动物蛋白法尼基转移酶抑制活性的新型N-(4-哌啶基)苯甲酰胺抗疟药。
Chem Pharm Bull (Tokyo). 2005 Oct;53(10):1324-6. doi: 10.1248/cpb.53.1324.
10
Protein farnesyltransferase and protein prenylation in Plasmodium falciparum.恶性疟原虫中的蛋白质法尼基转移酶和蛋白质异戊二烯化
J Biol Chem. 2002 Nov 1;277(44):42066-73. doi: 10.1074/jbc.M202860200. Epub 2002 Aug 22.
引用本文的文献
1
Antimicrobial Activity of Naphthyridine Derivatives.萘啶衍生物的抗菌活性。
Pharmaceuticals (Basel). 2024 Dec 17;17(12):1705. doi: 10.3390/ph17121705.
2
Naphthyridine Derivatives Induce Programmed Cell Death in .萘啶衍生物诱导……中的程序性细胞死亡
Pharmaceuticals (Basel). 2021 Oct 1;14(10):1013. doi: 10.3390/ph14101013.
3
Antioxidant and Larvicidal Activity of Areal Parts of against Malaria Vector .[植物名称]地上部分对疟疾媒介的抗氧化和杀幼虫活性
J Arthropod Borne Dis. 2018 Jun 13;12(2):119-126. eCollection 2018 Jun.
4
Global proteomic analysis of prenylated proteins in Plasmodium falciparum using an alkyne-modified isoprenoid analogue.利用炔基修饰的异戊烯基类似物对恶性疟原虫中的 prenylated 蛋白进行全局蛋白质组学分析。
Sci Rep. 2016 Dec 7;6:38615. doi: 10.1038/srep38615.
5
2D-QSAR study of some 2,5-diaminobenzophenone farnesyltransferase inhibitors by different chemometric methods.采用不同化学计量学方法对某些2,5-二氨基二苯甲酮法尼基转移酶抑制剂进行二维定量构效关系研究。
EXCLI J. 2015 Mar 30;14:484-95. doi: 10.17179/excli2015-177. eCollection 2015.
6
Prenyltransferase Inhibitors: Treating Human Ailments from Cancer to Parasitic Infections.异戊烯基转移酶抑制剂：治疗从癌症到寄生虫感染的人类疾病。
Medchemcomm. 2013 Mar;4(3):476-492. doi: 10.1039/C2MD20299A.
7
Exploring Drug Targets in Isoprenoid Biosynthetic Pathway for Plasmodium falciparum.探索恶性疟原虫类异戊二烯生物合成途径中的药物靶点。
Biochem Res Int. 2014;2014:657189. doi: 10.1155/2014/657189. Epub 2014 Apr 23.
8
An efficient sonochemical synthesis of novel Schiff's bases, thiazolidine, and pyrazolidine incorporating 1,8-naphthyridine moiety and their cytotoxic activity against HePG2 cell lines.一种高效的声化学合成方法，用于制备含1,8-萘啶部分的新型席夫碱、噻唑烷和吡唑烷及其对HePG2细胞系的细胞毒性活性。
ScientificWorldJournal. 2014 Feb 25;2014:587059. doi: 10.1155/2014/587059. eCollection 2014.
9
State of the art in African trypanosome drug discovery.非洲锥虫药物发现的最新进展。
Curr Top Med Chem. 2011;11(10):1255-74. doi: 10.2174/156802611795429167.
10
In vitro selection of Plasmodium falciparum drug-resistant parasite lines.体外筛选恶性疟原虫耐药虫株。
J Antimicrob Chemother. 2010 Mar;65(3):390-8. doi: 10.1093/jac/dkp449. Epub 2009 Dec 18.
本文引用的文献
1
Second generation tetrahydroquinoline-based protein farnesyltransferase inhibitors as antimalarials.基于第二代四氢喹啉的蛋白质法尼基转移酶抑制剂作为抗疟药物。
J Med Chem. 2007 Sep 20;50(19):4585-605. doi: 10.1021/jm0703340. Epub 2007 Aug 28.
2
Efficacy, pharmacokinetics, and metabolism of tetrahydroquinoline inhibitors of Plasmodium falciparum protein farnesyltransferase.恶性疟原虫蛋白法尼基转移酶的四氢喹啉抑制剂的疗效、药代动力学及代谢
Antimicrob Agents Chemother. 2007 Oct;51(10):3659-71. doi: 10.1128/AAC.00246-07. Epub 2007 Jul 2.
3
Innovative lead discovery strategies for tropical diseases.热带疾病的创新先导化合物发现策略。
Nat Rev Drug Discov. 2006 Nov;5(11):941-55. doi: 10.1038/nrd2144.
4
Therapeutic intervention based on protein prenylation and associated modifications.基于蛋白质异戊二烯化及相关修饰的治疗干预。
Nat Chem Biol. 2006 Oct;2(10):518-28. doi: 10.1038/nchembio818.
5
Thematic review series: lipid posttranslational modifications. Fighting parasitic disease by blocking protein farnesylation.专题综述系列：脂质翻译后修饰。通过阻断蛋白质法尼基化来对抗寄生虫病。
J Lipid Res. 2006 Feb;47(2):233-40. doi: 10.1194/jlr.R500016-JLR200. Epub 2005 Dec 7.
6
Protein farnesyl transferase inhibitors for the treatment of malaria and African trypanosomiasis.用于治疗疟疾和非洲锥虫病的蛋白质法尼基转移酶抑制剂。
Curr Opin Investig Drugs. 2005 Aug;6(8):791-7.
7
Protein farnesyltransferase inhibitors exhibit potent antimalarial activity.蛋白质法尼基转移酶抑制剂具有强大的抗疟活性。
J Med Chem. 2005 Jun 2;48(11):3704-13. doi: 10.1021/jm0491039.
8
Differential prenyl pyrophosphate binding to mammalian protein geranylgeranyltransferase-I and protein farnesyltransferase and its consequence on the specificity of protein prenylation.异戊烯焦磷酸与哺乳动物蛋白质香叶基香叶基转移酶-I和蛋白质法尼基转移酶的差异结合及其对蛋白质异戊烯化特异性的影响。
J Biol Chem. 1997 Feb 14;272(7):3944-52. doi: 10.1074/jbc.272.7.3944.
Zotero 插件