疟疾开源药物 Venture (疟疾和病原体) 药箱筛选，以发现针对曼氏利什曼原虫具有活性的新型化合物。
Screening of the Open-Source Medicines for Malaria Venture Malaria and Pathogen Boxes To Discover Novel Compounds with Activity against Balamuthia mandrillaris.
机构信息
Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, USA
Programa de Doctorado en Ciencias en Biotecnología, Departamento de Ciencias Agronómicas y Veterinarias, Instituto Tecnológico de Sonora, Obregon City, Sonora, Mexico.
出版信息
Antimicrob Agents Chemother. 2020 Apr 21;64(5). doi: 10.1128/AAC.02233-19.
Abstract
is an under-reported, pathogenic free-living amoeba that causes amoebic encephalitis (BAE) and cutaneous skin infections. Although cutaneous infections are not typically lethal, BAE with or without cutaneous involvement is usually fatal. This is due to the lack of drugs that are both efficacious and can cross the blood-brain barrier. We aimed to discover new leads for drug discovery by screening the open-source Medicines for Malaria Venture (MMV) Malaria Box and MMV Pathogen Box, with 800 compounds total. From an initial single point screen at 1 and 10 μM, we identified 54 hits that significantly inhibited the growth of Hits were reconfirmed in quantitative dose-response assays and 23 compounds (42.6%) were confirmed with activity greater than miltefosine, the current standard of care.
摘要
是一种报道较少的致病性自由生活阿米巴原虫，可引起阿米巴性脑炎（BAE）和皮肤皮肤感染。虽然皮肤感染通常不会致命，但伴有或不伴有皮肤受累的 BAE 通常是致命的。这是由于缺乏既有效又能穿过血脑屏障的药物。我们旨在通过筛选开源的疟疾药物 Venture（MMV）疟疾框和 MMV 病原体框来发现新药发现的新线索，总共 800 种化合物。从初始的 1 和 10μM 单点筛选中，我们确定了 54 个显著抑制生长的命中物。在定量剂量反应测定中重新确认了命中物，并且 23 种化合物（42.6％）的活性大于米替福新，米替福新是当前的护理标准。
相似文献
1
Screening of the Open-Source Medicines for Malaria Venture Malaria and Pathogen Boxes To Discover Novel Compounds with Activity against Balamuthia mandrillaris.疟疾开源药物 Venture (疟疾和病原体) 药箱筛选，以发现针对曼氏利什曼原虫具有活性的新型化合物。
Antimicrob Agents Chemother. 2020 Apr 21;64(5). doi: 10.1128/AAC.02233-19.
2
Functional Assessment of 2,177 U.S. and International Drugs Identifies the Quinoline Nitroxoline as a Potent Amoebicidal Agent against the Pathogen .对 2177 种美国和国际药物的功能评估确定了喹啉类硝呋太尔作为一种有效的抗病原体阿米巴药物。
mBio. 2018 Oct 30;9(5):e02051-18. doi: 10.1128/mBio.02051-18.
3
The transcriptome of Balamuthia mandrillaris trophozoites for structure-guided drug design.曼氏利什曼原虫滋养体的转录组用于基于结构的药物设计。
Sci Rep. 2021 Nov 4;11(1):21664. doi: 10.1038/s41598-021-99903-8.
4
Combined drug therapy in the management of granulomatous amoebic encephalitis due to Acanthamoeba spp., and Balamuthia mandrillaris.联合药物治疗棘阿米巴属和曼氏巴贝斯虫所致肉芽肿性阿米巴脑炎的管理
Exp Parasitol. 2014 Nov;145 Suppl:S115-20. doi: 10.1016/j.exppara.2014.03.025. Epub 2014 Apr 12.
5
Assessment of blood-brain barrier penetration of miltefosine used to treat a fatal case of granulomatous amebic encephalitis possibly caused by an unusual Balamuthia mandrillaris strain.用于治疗一例可能由罕见的曼氏巴兰姆希阿米巴菌株引起的肉芽肿性阿米巴脑炎致死病例的米替福新的血脑屏障穿透性评估。
Parasitol Res. 2015 Dec;114(12):4431-9. doi: 10.1007/s00436-015-4684-8. Epub 2015 Sep 2.
6
Discovery of Anti-Amoebic Inhibitors from Screening the MMV Pandemic Response Box on and .通过筛选MMV大流行应对药物库发现抗阿米巴抑制剂。 （你提供的原文中“on and.”表述不完整，我按合理理解进行了翻译）
Pathogens. 2020 Jun 16;9(6):476. doi: 10.3390/pathogens9060476.
7
Discovery of repurposing drug candidates for the treatment of diseases caused by pathogenic free-living amoebae.发现可再利用药物候选物用于治疗由致病性自由生活阿米巴引起的疾病。
PLoS Negl Trop Dis. 2020 Sep 24;14(9):e0008353. doi: 10.1371/journal.pntd.0008353. eCollection 2020 Sep.
8
A case of fatal amoebic encephalitis caused by Balamuthia mandrillaris, China.中国一起曼氏迭宫绦虫脑脓肿致死病例。
Infect Genet Evol. 2022 Jan;97:105190. doi: 10.1016/j.meegid.2021.105190. Epub 2021 Dec 22.
9
The isolation of Balamuthia mandrillaris from environmental sources from Peru.从秘鲁环境样本中分离曼氏巴尔通体。
Parasitol Res. 2014 Jul;113(7):2509-13. doi: 10.1007/s00436-014-3900-2. Epub 2014 Apr 30.
10
Laboratory testing of clinically approved drugs against Balamuthia mandrillaris.针对曼氏巴通体的临床批准药物的实验室检测。
World J Microbiol Biotechnol. 2014 Sep;30(9):2337-42. doi: 10.1007/s11274-014-1658-4. Epub 2014 May 30.
引用本文的文献
1
Cyclic Peptide Natural Product Inspired Inhibitors of the Free-Living Amoeba .环肽天然产物启发的自由生活阿米巴抑制剂
J Nat Prod. 2025 Feb 28;88(2):274-281. doi: 10.1021/acs.jnatprod.4c00834. Epub 2025 Feb 13.
2
Challenges and advances in the medical treatment of granulomatous amebic encephalitis.肉芽肿性阿米巴脑炎的医学治疗挑战与进展
Ther Adv Infect Dis. 2024 Feb 2;11:20499361241228340. doi: 10.1177/20499361241228340. eCollection 2024 Jan-Dec.
3
Identification of novel anti-amoebic pharmacophores from kinase inhibitor chemotypes.从激酶抑制剂化学类型中鉴定新型抗阿米巴药效基团。
Front Microbiol. 2023 May 10;14:1149145. doi: 10.3389/fmicb.2023.1149145. eCollection 2023.
4
Successful Treatment of Balamuthia mandrillaris Granulomatous Amebic Encephalitis with Nitroxoline.硝唑尼特成功治疗狒狒巴拉姆希阿米巴原虫肉芽肿性阿米巴脑炎。
Emerg Infect Dis. 2023 Jan;29(1):197-201. doi: 10.3201/eid2901.221531.
5
Antiamoebic Properties of Metabolites against and .代谢产物对[具体物种1]和[具体物种2]的抗阿米巴特性
Antibiotics (Basel). 2022 Apr 19;11(5):539. doi: 10.3390/antibiotics11050539.
6
Characterization of Glucokinases from Pathogenic Free-Living Amoebae.致病自由生活阿米巴中的葡萄糖激酶的特性。
Antimicrob Agents Chemother. 2022 Jun 21;66(6):e0237321. doi: 10.1128/aac.02373-21. Epub 2022 May 23.
7
Discovery of New Chemical Tools against via the MMV Pathogen Box.通过MMV病原体药物盒发现针对……的新型化学工具
Pharmaceuticals (Basel). 2021 Nov 24;14(12):1219. doi: 10.3390/ph14121219.
8
The transcriptome of Balamuthia mandrillaris trophozoites for structure-guided drug design.曼氏利什曼原虫滋养体的转录组用于基于结构的药物设计。
Sci Rep. 2021 Nov 4;11(1):21664. doi: 10.1038/s41598-021-99903-8.
9
Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro.探究间日疟原虫肝脏期寄生虫的独特化学敏感性，并在体外证明 8-氨基喹啉自由基治愈活性。
Sci Rep. 2021 Oct 7;11(1):19905. doi: 10.1038/s41598-021-99152-9.
10
Discovery of Anti-Amoebic Inhibitors from Screening the MMV Pandemic Response Box on and .通过筛选MMV大流行应对药物库发现抗阿米巴抑制剂。 （你提供的原文中“on and.”表述不完整，我按合理理解进行了翻译）
Pathogens. 2020 Jun 16;9(6):476. doi: 10.3390/pathogens9060476.
本文引用的文献
1
Functional Assessment of 2,177 U.S. and International Drugs Identifies the Quinoline Nitroxoline as a Potent Amoebicidal Agent against the Pathogen .对 2177 种美国和国际药物的功能评估确定了喹啉类硝呋太尔作为一种有效的抗病原体阿米巴药物。
mBio. 2018 Oct 30;9(5):e02051-18. doi: 10.1128/mBio.02051-18.
2
Phenotypic Screens Reveal Posaconazole as a Rapidly Acting Amebicidal Combination Partner for Treatment of Primary Amoebic Meningoencephalitis.表型筛选揭示泊沙康唑作为原发性阿米巴脑膜脑炎治疗的快速作用杀阿米巴组合伙伴。
J Infect Dis. 2019 Mar 15;219(7):1095-1103. doi: 10.1093/infdis/jiy622.
3
The Epidemiology and Clinical Features of Balamuthia mandrillaris Disease in the United States, 1974-2016.1974-2016 年美国狒狒曼氏阿米巴原虫病的流行病学和临床特征。
Clin Infect Dis. 2019 May 17;68(11):1815-1822. doi: 10.1093/cid/ciy813.
4
Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond.利用疟疾盒化合物库开展针对被忽视疾病及其他疾病的开源药物研发。
PLoS Pathog. 2016 Jul 28;12(7):e1005763. doi: 10.1371/journal.ppat.1005763. eCollection 2016 Jul.
5
Novel culture medium for the axenic growth of Balamuthia mandrillaris.用于曼氏巴贝斯虫无菌生长的新型培养基。
Diagn Microbiol Infect Dis. 2015 Aug;82(4):286-8. doi: 10.1016/j.diagmicrobio.2015.04.007. Epub 2015 Apr 28.
6
Bis-benzimidazole hits against Naegleria fowleri discovered with new high-throughput screens.通过新的高通量筛选发现的针对福氏耐格里阿米巴的双苯并咪唑类活性化合物。
Antimicrob Agents Chemother. 2015 Apr;59(4):2037-44. doi: 10.1128/AAC.05122-14. Epub 2015 Jan 20.
7
Genetic analysis among environmental strains of Balamuthia mandrillaris recovered from an artificial lagoon and from soil in Sonora, Mexico.从墨西哥索诺拉州的一个人工泻湖和土壤中分离出的曼氏巴贝斯虫环境菌株的遗传分析。
Exp Parasitol. 2014 Nov;145 Suppl:S57-61. doi: 10.1016/j.exppara.2014.07.007. Epub 2014 Jul 27.
8
Granulomatous amoebic encephalitis caused by Balamuthia mandrillaris in an immunocompetent girl.曼氏迭宫绦虫感染致免疫功能正常女童肉芽肿性阿米巴脑炎
World Neurosurg. 2012 Dec;78(6):715.e7-12. doi: 10.1016/j.wneu.2011.10.040. Epub 2011 Nov 1.
9
Opportunistic amoebae: challenges in prophylaxis and treatment.机会性变形虫：预防与治疗中的挑战
Drug Resist Updat. 2004 Feb;7(1):41-51. doi: 10.1016/j.drup.2004.01.002.
10
Balamuthia mandrillaris meningoencephalitis in an immunocompetent patient: an unusual clinical course and a favorable outcome.免疫功能正常患者的曼氏巴通体脑膜脑炎：不寻常的临床病程及良好预后
Arch Pathol Lab Med. 2004 Apr;128(4):466-8. doi: 10.5858/2004-128-466-BMMIAI.
Zotero 插件