Bhatnagar Ayushi, Pemawat Gangotri
Department of Chemistry, University College of Science, Mohanlal Sukhadia University, Udaipur, Rajasthan, India 313001.
Department of Chemistry, University College of Science, Mohanlal Sukhadia University, Udaipur, Rajasthan, India 313001.
Bioorg Chem. 2024 Dec;153:107780. doi: 10.1016/j.bioorg.2024.107780. Epub 2024 Sep 3.
Pyrimidine-based heterocyclic compounds are garnering substantial interest due to their essential role as a class of natural and synthetic molecules. These compounds show a diverse array of biologically relevant activities, making them highly prospective candidates for clinical translation as therapeutic agents in combating various diseases. Pyrimidine derivatives and their fused analogues, such as thienopyrimidines, pyrazolopyrimidines, pyridopyrimidines, and pyrimidopyrimidines, hold immense possibility in both anticancer and antibacterial research. These compounds exhibit notable efficacy by targeting protein kinases, which are crucial enzymes regulating fundamental cellular processes like metabolism, migration, division, and growth. Through enzyme inhibition, these derivatives disrupt key cellular signaling pathways, thereby affecting critical cellular functions and viability. The advantage lies in the ubiquity of the pyrimidine structure across various natural compounds, enabling interactions with enzymes, genetic material, and cellular components pivotal for chemical and biological processes. This interaction plays a central role in modulating vital biological activities, making pyrimidine-containing compounds indispensable in drug discovery. In the realm of anticancer therapy, these compounds strategically target key proteins like EGFR, important for aberrant cell growth. Fused pyrimidine motifs, exemplified by various drugs, are designed to inhibit EGFR, thereby impeding tumor progression. Moreover, these compounds influence potent antibacterial activity, interfering with microbial growth through mechanisms ranging from DNA replication inhibition to other vital cellular functions. This dual activity, targeting both cancer cells and microbial pathogens, underscores the versatility and potential of pyrimidine derivatives in medical applications. This review provides insights into the structural characteristics, synthesis methods, and significant medicinal applications of fused pyrimidine derivatives, highlighting their double role in combating cancer and bacterial infections.
基于嘧啶的杂环化合物因其作为一类天然和合成分子的重要作用而备受关注。这些化合物展现出一系列与生物学相关的多样活性，使其成为作为治疗剂对抗各种疾病进行临床转化的极具前景的候选物。嘧啶衍生物及其稠合类似物，如噻吩并嘧啶、吡唑并嘧啶、吡啶并嘧啶和嘧啶并嘧啶，在抗癌和抗菌研究中具有巨大潜力。这些化合物通过靶向蛋白激酶展现出显著疗效，蛋白激酶是调节诸如代谢、迁移、分裂和生长等基本细胞过程的关键酶。通过酶抑制，这些衍生物破坏关键的细胞信号通路，从而影响关键的细胞功能和活力。优势在于嘧啶结构在各种天然化合物中普遍存在，能够与对化学和生物过程至关重要的酶、遗传物质和细胞成分相互作用。这种相互作用在调节重要生物活性中起核心作用，使得含嘧啶化合物在药物发现中不可或缺。在抗癌治疗领域，这些化合物战略性地靶向如EGFR等对异常细胞生长重要的关键蛋白。以各种药物为例的稠合嘧啶基序旨在抑制EGFR，从而阻碍肿瘤进展。此外，这些化合物具有强大的抗菌活性，通过从抑制DNA复制到其他重要细胞功能的多种机制干扰微生物生长。这种针对癌细胞和微生物病原体的双重活性凸显了嘧啶衍生物在医学应用中的多功能性和潜力。本综述深入探讨了稠合嘧啶衍生物的结构特征、合成方法和重要的药用应用，强调了它们在对抗癌症和细菌感染中的双重作用。
