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深入了解治疗疟疾的临床候选药物及其靶蛋白的最新进展。

An insight into the recent development of the clinical candidates for the treatment of malaria and their target proteins.

机构信息

Drug Design and Synthesis Laboratory, Department of Chemistry, Jamia Millia Islamia (A Central University), New Delhi, 110025, India.

出版信息

Eur J Med Chem. 2021 Jan 15;210:112955. doi: 10.1016/j.ejmech.2020.112955. Epub 2020 Oct 22.

Abstract

Malaria is an endemic disease, prevalent in tropical and subtropical regions which cost half of million deaths annually. The eradication of malaria is one of the global health priority nevertheless, current therapeutic efforts seem to be insufficient due to the emergence of drug resistance towards most of the available drugs, even first-line treatment ACT, unavailability of the vaccine, and lack of drugs with a new mechanism of action. Intensification of antimalarial research in recent years has resulted into the development of single dose multistage therapeutic agents which has advantage of overcoming the antimalarial drug resistance. The present review explored the current progress in the development of new promising antimalarials against prominent target proteins that have the potential to be a clinical candidate. Here, we also reviewed different aspects of drug resistance and highlighted new drug candidates that are currently in a clinical trial or clinical development, along with a few other molecules with excellent antimalarial activity overs ACTs. The summarized scientific value of previous approaches and structural features of antimalarials related to the activity are highlighted that will be helpful for the development of next-generation antimalarials.

摘要

疟疾是一种地方性疾病,流行于热带和亚热带地区,每年造成 50 多万人死亡。尽管消除疟疾是全球卫生的重点之一,但由于大多数现有药物出现耐药性,甚至一线治疗 ACT 药物也无法获得,以及缺乏具有新作用机制的药物,目前的治疗努力似乎还不够。近年来,对抗疟研究的加强导致了单剂量多阶段治疗药物的开发,这种药物具有克服抗疟药物耐药性的优势。本综述探讨了针对有潜力成为临床候选药物的主要靶蛋白的新型有前途的抗疟药物的最新进展。在这里,我们还综述了耐药性的不同方面,并强调了目前处于临床试验或临床开发阶段的新候选药物,以及一些具有优于 ACTs 的抗疟活性的其他分子。突出了与活性相关的抗疟药物的先前方法的科学价值和结构特征,这将有助于开发下一代抗疟药物。

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