Suppr超能文献

正在研发的治疗弓形虫病的药物:进展、挑战与现状

Drugs in development for toxoplasmosis: advances, challenges, and current status.

作者信息

Alday P Holland, Doggett Joseph Stone

机构信息

Division of Infectious Diseases, Oregon Health & Science University.

Division of Infectious Diseases, Oregon Health & Science University; Portland Veterans Affairs Medical Center, Portland, OR, USA.

出版信息

Drug Des Devel Ther. 2017 Jan 25;11:273-293. doi: 10.2147/DDDT.S60973. eCollection 2017.

Abstract

causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis.

摘要

会引发致命和使人衰弱的脑部及眼部疾病。目前用于治疗弓形虫病的药物通常具有毒副作用,且需要持续数周甚至一年以上的长期疗程。治疗时间长以及疾病复发的风险部分归因于对组织囊肿缺乏疗效。开发更有效治疗弓形虫病的挑战包括降低毒性、在脑部和眼部达到治疗浓度、缩短疗程、从宿主体内清除组织囊肿、孕期安全性以及研发一种价格低廉且适用于世界资源匮乏地区的制剂。在过去十年中,在鉴定和开发治疗弓形虫病的新化合物方面取得了重大进展。与用于弓形虫病治疗的临床常用药物不同,这些化合物在临床前开发过程中已针对抗弓形虫病的疗效进行了优化。具有增强疗效以及解决弓形虫病独特方面特征的药物有可能极大地改善弓形虫病的治疗。本综述讨论了与药物设计相关的弓形虫病方面,以及弓形虫病临床前药物研究的进展、挑战和现状。

相似文献

1
Drugs in development for toxoplasmosis: advances, challenges, and current status.
Drug Des Devel Ther. 2017 Jan 25;11:273-293. doi: 10.2147/DDDT.S60973. eCollection 2017.
2
Recent progress on anti-Toxoplasma drugs discovery: Design, synthesis and screening.
Eur J Med Chem. 2019 Dec 1;183:111711. doi: 10.1016/j.ejmech.2019.111711. Epub 2019 Sep 19.
4
Two old drugs, NVP-AEW541 and GSK-J4, repurposed against the Toxoplasma gondii RH strain.
Parasit Vectors. 2020 May 11;13(1):242. doi: 10.1186/s13071-020-04094-2.
5
New antibacterials for the treatment of toxoplasmosis; a patent review.
Expert Opin Ther Pat. 2012 Mar;22(3):311-33. doi: 10.1517/13543776.2012.668886. Epub 2012 Mar 10.
6
Human toxoplasmosis-Searching for novel chemotherapeutics.
Biomed Pharmacother. 2016 Aug;82:677-84. doi: 10.1016/j.biopha.2016.05.041. Epub 2016 Jun 13.
7
[Advances in researches on mechanism of anti-Toxoplasma Chinese herbal medicine].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi. 2015 Oct;27(5):555-7, 559.
8
Structure-activity relationships of cytochrome inhibitors.
Expert Opin Drug Discov. 2022 Sep;17(9):997-1011. doi: 10.1080/17460441.2022.2096588. Epub 2022 Aug 8.
9
Screening for small molecule inhibitors of Toxoplasma gondii.
Expert Opin Drug Discov. 2012 Dec;7(12):1193-206. doi: 10.1517/17460441.2012.729036. Epub 2012 Sep 24.
10
Adenosine metabolism in Toxoplasma gondii: potential targets for chemotherapy.
Curr Pharm Des. 2007;13(6):581-97. doi: 10.2174/138161207780162836.

引用本文的文献

1
Protective Efficacy Induced by Virus-like Particles Expressing Dense Granule Protein 5 of .
Vaccines (Basel). 2025 Jul 24;13(8):787. doi: 10.3390/vaccines13080787.
2
Review of Toxoplasmosis: What We Still Need to Do.
Vet Sci. 2025 Aug 18;12(8):772. doi: 10.3390/vetsci12080772.
3
In Vivo Safety and Efficacy of Thiosemicarbazones in Experimental Mice Infected with Oocysts.
Biomedicines. 2025 Aug 1;13(8):1879. doi: 10.3390/biomedicines13081879.
4
Toxoplasma gondii-induced host's high secretion of 25-hydroxycholesterol for immunoprotection.
Parasit Vectors. 2025 Aug 4;18(1):333. doi: 10.1186/s13071-025-06890-0.
6
Computational Structural Comparison of Toxoplasma gondii CDPK1 and Human BUB1 kinases: Implications for Selective Inhibitor Design.
ACS Omega. 2025 Jun 11;10(24):25415-25431. doi: 10.1021/acsomega.5c00640. eCollection 2025 Jun 24.
7
Prophylactic Effect of Microwave Radiation on Tachyzoites of RH Strain: A Method for Partial Immunization in BALB/c Mice.
J Parasitol Res. 2025 May 27;2025:1666892. doi: 10.1155/japr/1666892. eCollection 2025.
8
The effectiveness of congenital toxoplasmosis treatment in minimizing hearing loss: A systematic review.
Sci Prog. 2025 Apr-Jun;108(2):368504251320834. doi: 10.1177/00368504251320834. Epub 2025 May 30.
10
Study of anti-Toxoplasma gondii effect of mPEG-PCL copolymeric loaded with pyrimethamine, in vitro.
AMB Express. 2025 May 2;15(1):69. doi: 10.1186/s13568-025-01876-8.

本文引用的文献

1
Genetic Evidence for Cytochrome b Qi Site Inhibition by 4(1H)-Quinolone-3-Diarylethers and Antimycin in Toxoplasma gondii.
Antimicrob Agents Chemother. 2017 Jan 24;61(2). doi: 10.1128/AAC.01866-16. Print 2017 Feb.
2
A Genome-wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes.
Cell. 2016 Sep 8;166(6):1423-1435.e12. doi: 10.1016/j.cell.2016.08.019. Epub 2016 Sep 2.
3
Apicoplast fatty acid synthesis is essential for pellicle formation at the end of cytokinesis in Toxoplasma gondii.
J Cell Sci. 2016 Sep 1;129(17):3320-31. doi: 10.1242/jcs.185223. Epub 2016 Jul 25.
7
Toxoplasma gondii infection: relationship with aggression in psychiatric subjects.
J Clin Psychiatry. 2016 Mar;77(3):334-41. doi: 10.4088/JCP.14m09621.
8
Follow-up of the 1977 Georgia Outbreak of Toxoplasmosis.
Am J Trop Med Hyg. 2016 Jun 1;94(6):1299-300. doi: 10.4269/ajtmh.15-0919. Epub 2016 Apr 4.
9
Failure of primary atovaquone prophylaxis for prevention of toxoplasmosis in hematopoietic cell transplant recipients.
Transpl Infect Dis. 2016 Jun;18(3):446-452. doi: 10.1111/tid.12532. Epub 2016 Jun 9.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验