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乳酸脱氢酶和苹果酸脱氢酶:药物研发研究中的潜在抗寄生虫靶点。

Lactate dehydrogenase and malate dehydrogenase: Potential antiparasitic targets for drug development studies.

作者信息

Kayamba Francis, Faya Mbuso, Pooe Ofentse Jacob, Kushwaha Babita, Kushwaha Narva Deshwar, Obakachi Vincent A, Nyamori Vincent O, Karpoormath Rajshekhar

机构信息

Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa; School of Science, Engineering and Technology, Mulungushi University, P.O. Box 80415, Kabwe, Zambia.

Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, South Africa.

出版信息

Bioorg Med Chem. 2021 Nov 15;50:116458. doi: 10.1016/j.bmc.2021.116458. Epub 2021 Oct 9.

Abstract

Parasitic diseases remain a major public health concern for humans, claiming millions of lives annually. Although different treatments are required for these diseases, drug usage is limited due to the development of resistance and toxicity, which necessitate alternative therapies. It has been shown in the literature that parasitic lactate dehydrogenases (LDH) and malate dehydrogenases (MDH) have unique pharmacological selective and specificity properties compared to other isoforms, thus highlighting them as viable therapeutic targets involved in aerobic and anaerobic glycolytic pathways. LDH and MDH are important therapeutic targets for invasive parasites because they play a critical role in the progression and development of parasitic diseases. Any strategy to impede these enzymes would be fatal to the parasites, paving the way to develop and discover novel antiparasitic agents. This review aims to highlight the importance of parasitic LDH and MDH as therapeutic drug targets in selected obligate apicoplast parasites. To the best of our knowledge, this review presents the first comprehensive review of LDH and MDH as potential antiparasitic targets for drug development studies.

摘要

寄生虫病仍然是人类主要的公共卫生问题,每年导致数百万人死亡。尽管这些疾病需要不同的治疗方法,但由于耐药性和毒性的发展,药物的使用受到限制,这就需要替代疗法。文献表明,与其他同工酶相比,寄生虫乳酸脱氢酶(LDH)和苹果酸脱氢酶(MDH)具有独特的药理选择性和特异性,因此突出了它们作为参与有氧和无氧糖酵解途径的可行治疗靶点。LDH和MDH是侵袭性寄生虫的重要治疗靶点,因为它们在寄生虫病的进展和发展中起关键作用。任何阻碍这些酶的策略对寄生虫来说都是致命的,这为开发和发现新型抗寄生虫药物铺平了道路。本综述旨在强调寄生虫LDH和MDH作为选定专性顶质体寄生虫治疗药物靶点的重要性。据我们所知,本综述首次全面综述了LDH和MDH作为药物开发研究潜在抗寄生虫靶点的情况。

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