一种用于开发强效杀锥虫剂的靶向递送策略。
A targeted delivery strategy for the development of potent trypanocides.
作者信息
Gordhan Heeren M, Milanes Jillian E, Qiu Yijian, Golden Jennifer E, Christensen Kenneth A, Morris James C, Whitehead Daniel C
机构信息
Department of Chemistry, Clemson University, Clemson, SC, USA.
Eukaryotic Pathogens Innovation Center, Department of Genetics and Biochemistry, Clemson University, Clemson, SC, USA.
出版信息
Chem Commun (Camb). 2017 Aug 11;53(62):8735-8738. doi: 10.1039/c7cc03378h. Epub 2017 Jul 20.
Abstract
A new drug delivery strategy was investigated for the development of potent anti-parasitic compounds against Trypanosoma brucei, the causative agent of African sleeping sickness. Thus, potent in vitro hexokinase inhibitors were rendered cytotoxic by appending a tripeptide peroxosomal targeting sequence that facilitated delivery of the molecular cargo to the appropriate organelle in the parasite.
摘要
针对非洲昏睡病的病原体布氏锥虫，研究了一种新的药物递送策略，以开发强效抗寄生虫化合物。因此，通过附加一个三肽过氧化物酶体靶向序列，使强效体外己糖激酶抑制剂具有细胞毒性，该序列有助于将分子货物递送至寄生虫中的适当细胞器。
相似文献
1
A targeted delivery strategy for the development of potent trypanocides.一种用于开发强效杀锥虫剂的靶向递送策略。
Chem Commun (Camb). 2017 Aug 11;53(62):8735-8738. doi: 10.1039/c7cc03378h. Epub 2017 Jul 20.
2
Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness.以布氏锥虫的HSP60/10伴侣蛋白系统为靶点作为治疗非洲昏睡病的一种策略。
Bioorg Med Chem Lett. 2016 Nov 1;26(21):5247-5253. doi: 10.1016/j.bmcl.2016.09.051. Epub 2016 Sep 22.
3
Discovery of 2-(1H-imidazo-2-yl)piperazines as a new class of potent and non-cytotoxic inhibitors of Trypanosoma brucei growth in vitro.发现2-(1H-咪唑-2-基)哌嗪类化合物作为一类新型的体外抑制布氏锥虫生长的强效且无细胞毒性的抑制剂。
Bioorg Med Chem Lett. 2018 Dec 15;28(23-24):3689-3692. doi: 10.1016/j.bmcl.2018.10.028. Epub 2018 Oct 22.
4
Chemotherapeutic strategies against Trypanosoma brucei: drug targets vs. drug targeting.针对布氏锥虫的化疗策略：药物靶点与药物靶向
Curr Pharm Des. 2007;13(6):555-67. doi: 10.2174/138161207780162809.
5
Autophagic-related cell death of Trypanosoma brucei induced by bacteriocin AS-48.细菌素 AS-48 诱导的布氏锥虫自噬相关细胞死亡。
Int J Parasitol Drugs Drug Resist. 2018 Aug;8(2):203-212. doi: 10.1016/j.ijpddr.2018.03.002. Epub 2018 Mar 12.
6
Design, synthesis and biological evaluation of potent azadipeptide nitrile inhibitors and activity-based probes as promising anti-Trypanosoma brucei agents.设计、合成及生物评价强效瑞香烷肽腈类抑制剂及基于活性的探针作为有前景的抗布氏锥虫药物。
Chemistry. 2012 May 21;18(21):6528-41. doi: 10.1002/chem.201103322. Epub 2012 Apr 4.
7
Sphingosine Kinase Regulates Microtubule Dynamics and Organelle Positioning Necessary for Proper G1/S Cell Cycle Transition in Trypanosoma brucei.鞘氨醇激酶调节布氏锥虫中G1/S细胞周期正常转换所必需的微管动力学和细胞器定位。
mBio. 2015 Oct 6;6(5):e01291-15. doi: 10.1128/mBio.01291-15.
8
Drug resistance in Trypanosoma brucei spp., the causative agents of sleeping sickness in man and nagana in cattle.布氏锥虫属（Trypanosoma brucei spp.）中的耐药性，布氏锥虫属是人类昏睡病和牛那加那病的病原体。
Microbes Infect. 2001 Jul;3(9):763-70. doi: 10.1016/s1286-4579(01)01432-0.
9
Inhibition of trypanosome alternative oxidase without its N-terminal mitochondrial targeting signal (ΔMTS-TAO) by cationic and non-cationic 4-hydroxybenzoate and 4-alkoxybenzaldehyde derivatives active against T. brucei and T. congolense.对布氏锥虫和刚果锥虫具有活性的阳离子和非阳离子4-羟基苯甲酸酯及4-烷氧基苯甲醛衍生物对没有N端线粒体靶向信号的锥虫交替氧化酶（ΔMTS-TAO）的抑制作用
Eur J Med Chem. 2018 Apr 25;150:385-402. doi: 10.1016/j.ejmech.2018.02.075. Epub 2018 Feb 26.
10
Trypanosoma brucei: effects of methoprene and other isoprenoid compounds on procyclic and bloodstream forms in vitro and in mice.布氏锥虫：甲氧普烯及其他类异戊二烯化合物对体外培养及小鼠体内前循环型和血流型布氏锥虫的影响
Exp Parasitol. 1997 Nov;87(3):229-36. doi: 10.1006/expr.1997.4196.
引用本文的文献
1
FRET Flow Cytometry-Based High Throughput Screening Assay To Identify Disrupters of Glucose Levels in Trypanosoma brucei.基于荧光共振能量转移流式细胞术的高通量筛选试验，用于鉴定布氏锥虫葡萄糖水平的干扰物。
ACS Infect Dis. 2018 Jul 13;4(7):1058-1066. doi: 10.1021/acsinfecdis.8b00058. Epub 2018 May 14.
本文引用的文献
1
Optimization and Evaluation of Antiparasitic Benzamidobenzoic Acids as Inhibitors of Kinetoplastid Hexokinase 1.作为动质体己糖激酶1抑制剂的抗寄生虫苯甲酰苯甲酸的优化与评价
ChemMedChem. 2017 Dec 7;12(23):1994-2005. doi: 10.1002/cmdc.201700592. Epub 2017 Nov 16.
2
Exploring the mode of action of ebselen in Trypanosoma brucei hexokinase inhibition.探讨依布硒啉抑制布氏锥虫己糖激酶作用模式。
Int J Parasitol Drugs Drug Resist. 2013 Sep 12;3:154-60. doi: 10.1016/j.ijpddr.2013.08.002. eCollection 2013 Dec.
3
Peptide-targeted delivery of a pH sensor for quantitative measurements of intraglycosomal pH in live Trypanosoma brucei.肽靶向递送 pH 传感器，用于定量测量活布鲁氏锥虫糖苷体内部的 pH 值。
Biochemistry. 2013 May 28;52(21):3629-37. doi: 10.1021/bi400029m. Epub 2013 May 17.
4
Identification and validation of Trypanosoma cruzi's glycosomal adenylate kinase containing a peroxisomal targeting signal.鉴定和验证含有过氧化物酶体靶向信号的克氏锥虫糖体腺苷酸激酶。
Exp Parasitol. 2012 Apr;130(4):408-11. doi: 10.1016/j.exppara.2012.01.020. Epub 2012 Feb 7.
5
Glycerol 3-phosphate alters Trypanosoma brucei hexokinase activity in response to environmental change.甘油-3-磷酸可改变环境变化时布氏锥虫己糖激酶的活性。
J Biol Chem. 2011 Sep 23;286(38):33150-7. doi: 10.1074/jbc.M111.235705. Epub 2011 Aug 3.
6
Quercetin, a fluorescent bioflavanoid, inhibits Trypanosoma brucei hexokinase 1.槲皮素，一种荧光类黄酮，可抑制布氏锥虫己糖激酶 1。
Exp Parasitol. 2011 Feb;127(2):423-8. doi: 10.1016/j.exppara.2010.10.011. Epub 2010 Nov 11.
7
A target-based high throughput screen yields Trypanosoma brucei hexokinase small molecule inhibitors with antiparasitic activity.基于靶标的高通量筛选得到具有抗寄生虫活性的布氏锥虫己糖激酶小分子抑制剂。
PLoS Negl Trop Dis. 2010 Apr 13;4(4):e659. doi: 10.1371/journal.pntd.0000659.
8
Spelling Pneumocystis jirovecii.拼写：耶氏肺孢子菌。
Emerg Infect Dis. 2009 Mar;15(3):506. doi: 10.3201/eid1503.081060.
9
The anti-trypanosomal agent lonidamine inhibits Trypanosoma brucei hexokinase 1.抗锥虫药氯尼达明可抑制布氏锥虫己糖激酶1。
Mol Biochem Parasitol. 2008 Apr;158(2):202-7. doi: 10.1016/j.molbiopara.2007.12.013. Epub 2008 Jan 3.
10
Fast conventional Fmoc solid-phase peptide synthesis with HCTU.使用HCTU的快速常规Fmoc固相肽合成法。
J Pept Sci. 2008 Jan;14(1):97-101. doi: 10.1002/psc.921.
Zotero 插件