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疟疾中的氧化还原调控:当前概念和药物治疗意义。

Redox regulation in malaria: current concepts and pharmacotherapeutic implications.

机构信息

Division of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India.

出版信息

Curr Med Chem. 2012;19(10):1475-503. doi: 10.2174/092986712799828328.

Abstract

Malaria imposes a serious threat to human and becomes more prevalent due to the emergence of drug resistant parasite. Understanding of the underlying mechanism of drug resistance and identification of novel drug targets are key effective processes for the management of malaria. Malaria parasite is highly susceptible to oxidative stress but lives in a pro-oxidant rich environment containing oxygen and iron, which produce a large amount of reactive oxygen species. Management of oxidative stress in malaria parasite is tightly regulated through active redox and antioxidant defense systems. The elevation of oxidative stress as a result of inhibition of any component of this defense system leads to redox imbalance and ultimately parasite death. Therefore, redox system plays an indispensable role for the survival of parasite within the host. Identification of key molecules, which disrupt parasite redox balance by altering key redox reactions and promote oxidative stress in parasites, would be an effective approach to develop novel antimalarial drugs. During the last few decades, contributions by researchers around the globe provide even better understanding of redox biology of malaria parasite. Here, in this review, we are highlighting the knowledge gathered so far regarding the essential redox-active processes and their components in malaria parasite to overcome elevated oxidative insults. We have also given maximum efforts to enlist currently used redox-active antimalarials, their mode of action and pharmacotherapeutic implications.

摘要

疟疾对人类构成严重威胁,由于抗药性寄生虫的出现,疟疾变得更加普遍。了解耐药性的潜在机制和确定新的药物靶点是管理疟疾的关键有效过程。疟原虫对氧化应激高度敏感,但生活在富含氧气和铁的促氧化剂环境中,会产生大量的活性氧。疟原虫通过积极的氧化还原和抗氧化防御系统来严格控制氧化应激的管理。任何防御系统成分的抑制都会导致氧化应激升高,从而导致氧化还原失衡,最终导致寄生虫死亡。因此,氧化还原系统对于寄生虫在宿主中的生存起着不可或缺的作用。鉴定出通过改变关键氧化还原反应破坏寄生虫氧化还原平衡并促进寄生虫内氧化应激的关键分子,将是开发新型抗疟药物的有效方法。在过去的几十年中,全球研究人员的贡献使我们对疟原虫的氧化还原生物学有了更好的理解。在这里,我们重点介绍了迄今为止在疟原虫中获得的关于基本氧化还原活性过程及其成分的知识,以克服升高的氧化应激。我们还尽最大努力列出了目前使用的氧化还原活性抗疟药物、它们的作用模式和药物治疗意义。

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