抗疟药物研发中的表型筛选
Phenotypic Screens in Antimalarial Drug Discovery.
作者信息
Hovlid Marisa L, Winzeler Elizabeth A
机构信息
School of Medicine, Department of Pediatrics, Division of Host-Microbe Systems and Therapeutics, University of California, San Diego (UCSD), 9500 Gilman Drive, La Jolla, CA 92093, USA.
School of Medicine, Department of Pediatrics, Division of Host-Microbe Systems and Therapeutics, University of California, San Diego (UCSD), 9500 Gilman Drive, La Jolla, CA 92093, USA.
出版信息
Trends Parasitol. 2016 Sep;32(9):697-707. doi: 10.1016/j.pt.2016.04.014. Epub 2016 May 27.
Abstract
Phenotypic high-throughput screens are a valuable tool for identifying new chemical compounds with antimalarial activity. Traditionally, these screens have focused solely on the symptomatic asexual blood stage of the parasite life cycle; however, to discover new medicines for malaria treatment and prevention, robust screening technologies against other parasite life-cycle stages are required. This review highlights recent advances and progress toward phenotypic screening methodologies over the past several years, with a focus on exoerythrocytic stage screens.
摘要
表型高通量筛选是鉴定具有抗疟活性新化合物的宝贵工具。传统上，这些筛选仅聚焦于寄生虫生命周期中有症状的无性血液阶段；然而，为了发现用于疟疾治疗和预防的新药，需要针对其他寄生虫生命周期阶段的强大筛选技术。本综述重点介绍了过去几年表型筛选方法的最新进展，尤其关注红细胞外期筛选。
相似文献
1
Phenotypic Screens in Antimalarial Drug Discovery.
Trends Parasitol. 2016 Sep;32(9):697-707. doi: 10.1016/j.pt.2016.04.014. Epub 2016 May 27.
2
Phenotypic Screening of Small Molecules with Antimalarial Activity for Three Different Parasitic Life Stages.
Methods Mol Biol. 2018;1787:41-52. doi: 10.1007/978-1-4939-7847-2_3.
3
Probing the Open Global Health Chemical Diversity Library for Multistage-Active Starting Points for Next-Generation Antimalarials.
ACS Infect Dis. 2020 Apr 10;6(4):613-628. doi: 10.1021/acsinfecdis.9b00482. Epub 2020 Mar 4.
4
4-Nitro styrylquinoline is an antimalarial inhibiting multiple stages of Plasmodium falciparum asexual life cycle.
Int J Parasitol Drugs Drug Resist. 2017 Apr;7(1):120-129. doi: 10.1016/j.ijpddr.2017.02.002. Epub 2017 Feb 21.
5
Discovery of carbohybrid-based 2-aminopyrimidine analogues as a new class of rapid-acting antimalarial agents using image-based cytological profiling assay.
J Med Chem. 2014 Sep 11;57(17):7425-34. doi: 10.1021/jm5009693. Epub 2014 Aug 26.
6
Progressing the global antimalarial portfolio: finding drugs which target multiple Plasmodium life stages.
Parasitology. 2014 Jan;141(1):66-76. doi: 10.1017/S0031182013000747. Epub 2013 Jun 10.
7
Multistage inhibitors of the malaria parasite: Emerging hope for chemoprotection and malaria eradication.
Med Res Rev. 2018 Sep;38(5):1511-1535. doi: 10.1002/med.21486. Epub 2018 Jan 26.
8
Antiapicoplast and gametocytocidal screening to identify the mechanisms of action of compounds within the malaria box.
Antimicrob Agents Chemother. 2014;58(2):811-9. doi: 10.1128/AAC.01500-13. Epub 2013 Nov 18.
9
A New Set of Chemical Starting Points with Plasmodium falciparum Transmission-Blocking Potential for Antimalarial Drug Discovery.
PLoS One. 2015 Aug 28;10(8):e0135139. doi: 10.1371/journal.pone.0135139. eCollection 2015.
10
Whole-cell in vitro screening for gametocytocidal compounds.
Future Med Chem. 2012 Dec;4(18):2337-60. doi: 10.4155/fmc.12.188.
引用本文的文献
1
Development and experimental validation of a machine learning model for the prediction of new antimalarials.
BMC Chem. 2025 Jan 30;19(1):28. doi: 10.1186/s13065-025-01395-4.
2
Structure-Based Discovery and Development of Highly Potent Dihydroorotate Dehydrogenase Inhibitors for Malaria Chemoprevention.
J Med Chem. 2025 Jan 9;68(1):590-637. doi: 10.1021/acs.jmedchem.4c02394. Epub 2024 Dec 22.
3
Human liver organoids are susceptible to Plasmodium vivax infection.
Malar J. 2024 Dec 5;23(1):368. doi: 10.1186/s12936-024-05202-8.
4
Global Health Priority Box─Proactive Pandemic Preparedness.
ACS Infect Dis. 2024 Dec 13;10(12):4030-4039. doi: 10.1021/acsinfecdis.4c00700. Epub 2024 Nov 3.
5
A high content imaging assay for identification of specific inhibitors of native liver stage protein synthesis.
Antimicrob Agents Chemother. 2024 Oct 8;68(10):e0079324. doi: 10.1128/aac.00793-24. Epub 2024 Sep 10.
6
Inhibition of falcilysin from Plasmodium falciparum by interference with its closed-to-open dynamic transition.
Commun Biol. 2024 Aug 31;7(1):1070. doi: 10.1038/s42003-024-06774-6.
7
CACTI: an in silico chemical analysis tool through the integration of chemogenomic data and clustering analysis.
J Cheminform. 2024 Jul 24;16(1):84. doi: 10.1186/s13321-024-00885-2.
8
A high content imaging assay for identification of specific inhibitors of native liver stage protein synthesis.
bioRxiv. 2024 May 29:2024.05.29.596519. doi: 10.1101/2024.05.29.596519.
9
Differential effects of translation inhibitors on liver stage parasites.
Life Sci Alliance. 2024 Apr 4;7(6). doi: 10.26508/lsa.202302540. Print 2024 Jun.
10
Recent advances of phenotypic screening strategies in the application of anti-influenza virus drug discovery.
RSC Med Chem. 2023 Nov 9;15(1):70-80. doi: 10.1039/d3md00513e. eCollection 2024 Jan 25.
本文引用的文献
1
Plasmodium falciparum Cyclic Amine Resistance Locus (PfCARL), a Resistance Mechanism for Two Distinct Compound Classes.
ACS Infect Dis. 2016 Nov 11;2(11):816-826. doi: 10.1021/acsinfecdis.6b00025. Epub 2016 Apr 7.
2
High-Throughput Luciferase-Based Assay for the Discovery of Therapeutics That Prevent Malaria.
ACS Infect Dis. 2016 Apr 8;2(4):281-293. doi: 10.1021/acsinfecdis.5b00143. Epub 2016 Feb 10.
3
High-Throughput Assay and Discovery of Small Molecules that Interrupt Malaria Transmission.
Cell Host Microbe. 2016 Jan 13;19(1):114-26. doi: 10.1016/j.chom.2015.12.001. Epub 2015 Dec 31.
4
A semi-automated luminescence based standard membrane feeding assay identifies novel small molecules that inhibit transmission of malaria parasites by mosquitoes.
Sci Rep. 2015 Dec 21;5:18704. doi: 10.1038/srep18704.
5
Discovery of Dual-Stage Malaria Inhibitors with New Targets.
Antimicrob Agents Chemother. 2015 Dec 14;60(3):1430-7. doi: 10.1128/AAC.02110-15.
6
A simple and predictive phenotypic High Content Imaging assay for Plasmodium falciparum mature gametocytes to identify malaria transmission blocking compounds.
Sci Rep. 2015 Nov 10;5:16414. doi: 10.1038/srep16414.
7
Identifying rapidly parasiticidal anti-malarial drugs using a simple and reliable in vitro parasite viability fast assay.
Malar J. 2015 Nov 5;14:441. doi: 10.1186/s12936-015-0962-2.
8
Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine.
N Engl J Med. 2015 Nov 19;373(21):2025-2037. doi: 10.1056/NEJMoa1505819. Epub 2015 Oct 21.
9
Landmark green light for Mosquirix malaria vaccine.
Nat Biotechnol. 2015 Oct;33(10):1015-6. doi: 10.1038/nbt1015-1015.
10
Hit and lead criteria in drug discovery for infectious diseases of the developing world.
Nat Rev Drug Discov. 2015 Nov;14(11):751-8. doi: 10.1038/nrd4683. Epub 2015 Oct 5.
Zotero 插件