Alizadeh Seyedeh Roya, Ebrahimzadeh Mohammad Ali
Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran.
Mini Rev Med Chem. 2021;21(17):2584-2611. doi: 10.2174/1389557521666210126143558.
Heterocyclic compounds play a critical role in medicinal chemistry, and many available drugs contain heterocyclic rings. A six-membered heterocyclic compound, pyridine, showed various applications, including being an important solvent, reagent, and precursor in agrochemicals and pharmaceuticals. Due to the increase in drug resistance, there is an apparent medical need to develop new antiviral agents. Various derivatives of pyridine scaffold display broad biological activities such as anti-microbial, antiviral, antioxidant, anti-diabetic, anti-cancer, anti-malarial, analgesic, and antiinflammatory activities. Furthermore, they display psychopharmacological, antagonistic, anti-amoebic agents, and anti-thrombic activities. Due to the high importance of pyridine derivatives, in the present review, we tried to collect and classify many pyridine derivatives based on their structures from 2000 to 2020. Pyridine derivatives were classified into two general categories, including pyridine containing heterocycles and pyridine fused rings. The structure-activity relationship (SAR) and the action mechanism of derivatives were also investigated. According to the recent studies, these derivatives exhibited good antiviral activity against different types of viruses such as the human immunodeficiency viruses (HIV), the hepatitis C virus (HCV), the hepatitis B virus (HBV), respiratory syncytial virus (RSV), and cytomegalovirus (CMV). These derivatives inhibited viral application with different action mechanism such as RT inhibition, polymerase inhibition, inhibition of RNase H activity, inhibition of maturation, inhibition of the viral thymidine kinase, AAK1 (Adaptor-Associated Kinase 1) inhibition, GAK (Cyclin G-associated kinase) inhibition, inhibition of post-integrational event, inhibition of HDAC6, CCR5 antagonistic activity, DNA and RNA replication inhibition, gene expression inhibition, cellular NF-jB signaling pathway and neuraminidase (NA) inhibition, protein synthesis inhibition, and generally inhibition of viral replication cycle. This paper summarized the past and present results about the discovery of novel lead compounds with good antiviral activity. Studies exhibited that almost all of the evaluations were performed by way of in vitro testing. It is necessary to investigate in vivo and clinical testing for better evaluations in the future. We believe that pyridine derivatives can be used as promising antiviral agents and more broad investigations in this field need to be performed.
杂环化合物在药物化学中起着关键作用，许多现有药物都含有杂环。一种六元杂环化合物吡啶具有多种应用，包括作为重要的溶剂、试剂以及农用化学品和药物中的前体。由于耐药性的增加，显然有医学需求来开发新的抗病毒药物。吡啶骨架的各种衍生物表现出广泛的生物活性，如抗菌、抗病毒、抗氧化、抗糖尿病、抗癌、抗疟疾、止痛和抗炎活性。此外，它们还具有精神药理学、拮抗、抗阿米巴和抗血栓活性。由于吡啶衍生物的高度重要性，在本综述中，我们试图收集并根据其结构对2000年至2020年期间的许多吡啶衍生物进行分类。吡啶衍生物分为两大类，包括含吡啶杂环和吡啶稠环。还研究了衍生物的构效关系（SAR）和作用机制。根据最近的研究，这些衍生物对不同类型的病毒表现出良好的抗病毒活性，如人类免疫缺陷病毒（HIV）、丙型肝炎病毒（HCV）、乙型肝炎病毒（HBV）、呼吸道合胞病毒（RSV）和巨细胞病毒（CMV）。这些衍生物通过不同的作用机制抑制病毒作用，如逆转录酶抑制、聚合酶抑制、核糖核酸酶H活性抑制、成熟抑制、病毒胸苷激酶抑制、AAK1（衔接蛋白相关激酶1）抑制、GAK（细胞周期蛋白G相关激酶）抑制、整合后事件抑制、HDAC6抑制、CCR5拮抗活性、DNA和RNA复制抑制、基因表达抑制、细胞NF-κB信号通路和神经氨酸酶（NA）抑制、蛋白质合成抑制以及一般的病毒复制周期抑制。本文总结了关于发现具有良好抗病毒活性的新型先导化合物的过去和现在的结果。研究表明，几乎所有的评估都是通过体外试验进行的。未来有必要进行体内和临床试验以进行更好的评估。我们相信吡啶衍生物可以用作有前景的抗病毒药物，并且需要在该领域进行更广泛的研究。
