抗疟药物发现的创新:新的靶点和线索。

IF 3 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Neha Jeena, Lata Panicker, Inshad Ali Khan
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引用次数: 0

摘要

由于缺乏有效的治疗方案和疟原虫耐药菌株的增加,疟疾控制受到严重阻碍。尽管缺乏可靠的疫苗,治疗性应用抗疟疾药物仍然是控制和预防疟疾的主要战略。然而,大多数现有的抗疟药物靶向寄生虫生命周期的血液阶段,可能无法有效消除肝脏阶段的寄生虫,从而限制了其完全清除寄生虫的功效。迫切需要具有创新作用机制的新型抗疟药,这对预防重大公共卫生危机至关重要。开发新的抗疟药物包括优化现有化合物和设计针对疟原虫独特生物途径的新分子。本文综述了有前景的药物靶点,包括血红素解毒、食物液泡功能、线粒体、蛋白激酶、顶质体途径、核酸生物合成、脂肪酸代谢、电子传递链(ETC)和p型atp酶。讨论了针对这些机制的主要候选药物,强调了它们作为下一代抗疟疾药物的潜力。此外,我们还提供临床有效的靶点和处于不同临床开发阶段的抗疟候选药物的最新进展。关注疟疾转运蛋白、蛋白质相互作用网络和底物谱的新兴治疗策略为药物发现提供了新的途径。更深入地了解这些途径可以提高药物疗效,减轻耐药性,并支持开发持久的抗疟疾疗法。本文旨在对抗疟药物的发展现状和未来防治疟疾的方向进行综述。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Innovations in Antimalarial Drug Discovery: New Targets and Leads.

Malaria control is severely hindered by a lack of effective treatment options and the rise of drug-resistant strains of the parasite. Despite the absence of a reliable vaccine, the thera-peutic application of antimalarial drugs remains the primary strategy for controlling and prevent-ing malaria. However, most existing antimalarial drugs target the blood stage of the parasite's lifecycle and may not effectively eliminate liver-stage parasites, limiting their efficacy in com-plete parasite clearance. The urgent need for novel antimalarial drugs with innovative mecha-nisms of action is critical to preventing a major public health crisis. Developing new antimalarial drugs involves both optimizing existing compounds and designing novel molecules that target unique biological pathways in Plasmodium. This review explores promising drug targets, includ-ing heme detoxification, food vacuole function, mitochondria, protein kinases, apicoplast path-ways, nucleic acid biosynthesis, fatty acid metabolism, the electron transport chain (ETC), and P-Type ATPases. Lead candidates targeting these mechanisms are discussed, highlighting their po-tential as next-generation antimalarial agents. Additionally, we provide updates on clinically vali-dated targets and the progress of antimalarial drug candidates in different stages of clinical devel-opment. Emerging therapeutic strategies focusing on malarial transporters, protein interaction networks, and substrate repertoires offer new avenues for drug discovery. A deeper understanding of these pathways can enhance drug efficacy, mitigate resistance, and support the development of long-lasting antimalarial therapies. This review aims to provide insights into the current landscape of antimalarial drug development and future directions for combating malaria.

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来源期刊
Current drug targets
Current drug targets 医学-药学
CiteScore
6.20
自引率
0.00%
发文量
127
审稿时长
3-8 weeks
期刊介绍: Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Current Drug Targets publishes guest edited thematic issues written by leaders in the field covering a range of current topics of drug targets. The journal also accepts for publication mini- & full-length review articles and drug clinical trial studies. As the discovery, identification, characterization and validation of novel human drug targets for drug discovery continues to grow; this journal is essential reading for all pharmaceutical scientists involved in drug discovery and development.
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