吡啶和嘧啶杂化物作为抗疟药物发现的特殊支架:最新进展。

IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL Bioorganic & Medicinal Chemistry Letters Pub Date : 2024-10-18 DOI:10.1016/j.bmcl.2024.129992
Lekkala Ravindar , Siti Aishah Hasbullah , K.P. Rakesh , Saki Raheem , Norzila Ismail , Lau Yee Ling , Nurul Izzaty Hassan
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引用次数: 0

摘要

疟疾继续对全球健康构成重大威胁,而抗药性菌株的出现又加剧了这一威胁,因此迫切需要开发新的治疗方案。由于吡啶和嘧啶在治疗疟疾方面的巨大生物活性,它们已成为药物研究的焦点。吡啶和嘧啶的混合物为开发有效的抗疟药物提供了一个新颖而有前景的途径。这些杂交化合物具有克服耐药性的能力,为治疗疟疾的这一关键障碍提供了潜在的解决方案。通过靶向多种途径,这些杂交化合物降低了抗药性产生的可能性,为抗击耐药性疟疾菌株提供了一种前景广阔的策略。这篇综述重点介绍了 2018 年吡啶和嘧啶杂化化合物结构优化方面的最新进展,着重介绍了已被证明能提高抗疟活性的修饰。结构-活性研究阐明了药效、选择性和药代动力学所需的基本特征。分子对接和虚拟筛选加速了具有更强活性特征的新型化合物的鉴定。这种分析有助于开发出最有效的吡啶和嘧啶混合物作为抗疟药物。
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Pyridine and Pyrimidine hybrids as privileged scaffolds in antimalarial drug discovery: A recent development
Malaria continues to pose a significant threat to global health, which is exacerbated by the emergence of drug-resistant strains, necessitating the urgent development of new therapeutic options. Due to their substantial bioactivity in treating malaria, pyridine and pyrimidine have become the focal point of drug research. Hybrids of pyridine and pyrimidine offer a novel and promising avenue for developing effective antimalarial agents. The ability of these hybrids to overcome drug resistance is tinted, offering a potential solution to this critical obstacle in the treatment of malaria. By targeting multiple pathways, these hybrid compounds reduce the likelihood of resistance development, providing a promising strategy for combating drug-resistant strains of malaria. The review focuses on the most recent developments in 2018 in the structural optimization of pyridine and pyrimidine hybrid compounds, highlighting modifications that have been shown to improve antimalarial activity. Structure-activity studies have elucidated the essential characteristics required for potency, selectivity, and pharmacokinetics. Molecular docking and virtual screening expedite the identification of novel compounds with enhanced activity profiles. This analysis could aid in developing the most effective pyridine and pyrimidine hybrids as antimalarial agents.
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来源期刊
CiteScore
5.70
自引率
3.70%
发文量
463
审稿时长
27 days
期刊介绍: Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.
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