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生物有机金属化合物作为撒哈拉以南非洲地区抗血吸虫病的新型药物靶点:吡喹酮的替代品?

Bioorganometallic Compounds as Novel Drug Targets against Schistosomiasis in Sub-Saharan Africa: An alternative to Praziquantel?

作者信息

Ndamse Cuma Cumisa, Masamba Priscilla, Kappo Abidemi Paul

机构信息

Molecular Biophysics and Structural Biology Group, Department of Biochemistry, University of Johannesburg, Kingsway Campus, Auckland Park 2006, South Africa.

出版信息

Adv Pharm Bull. 2022 Mar;12(2):283-297. doi: 10.34172/apb.2022.029. Epub 2021 May 30.

Abstract

Human schistosomiasis is a disease that mostly plagues the destitute of various tropical and sub-tropical countries, particularly in sub-Saharan Africa (SSA) and South America. It has significant effects on various health and economic-related matters. Globally, the burden of schistosomiasis has been controlled with a single chemotherapeutic drug, praziquantel (PZQ), which has recently demonstrated several clinical issues, including its inability to destroy juvenile schistosome worms and drug resistance because of its extensive use. The use of organometallic moieties in biological and medicinal chemistry has developed greatly and has led to their use in various anti-cancer and anti-infectious agents. The abundance of a range of organometallic compounds that can cause damage to the parasite has received tremendous feedback, with many already at clinical trials. The distinct redox biology of the schistosome parasite is a vulnerable element to the survival of the worm and has steered attempts toward the use of redox-directed bioorganometallic compounds. Disruption of the schistosome redox homeostasis through organometallic ions provides a novel drug target that could be used in overcoming the drawbacks of the mainstream drug and one that could possibly bypass the emergence of drug resistance.

摘要

人类血吸虫病是一种主要困扰热带和亚热带国家贫困人口的疾病,特别是在撒哈拉以南非洲(SSA)和南美洲。它对各种健康和经济相关问题有重大影响。在全球范围内,血吸虫病的负担一直通过单一化疗药物吡喹酮(PZQ)来控制,该药物最近出现了几个临床问题,包括无法杀死幼年血吸虫以及由于广泛使用而产生的耐药性。生物和药物化学中有机金属部分的应用有了很大发展,并导致其被用于各种抗癌和抗感染药物中。一系列能够对寄生虫造成损害的有机金属化合物受到了极大关注,许多已进入临床试验阶段。血吸虫独特的氧化还原生物学是其生存的一个脆弱因素,这促使人们尝试使用氧化还原导向的生物有机金属化合物。通过有机金属离子破坏血吸虫的氧化还原稳态提供了一个新的药物靶点,可用于克服主流药物的缺点,并有可能避免耐药性的出现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c599/9106956/8b6ea1489493/apb-12-283-g001.jpg

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