Deeva E G, Pavlovskaia Ia V, Kiselev O I, Kiselev V I, Piotrovskiĭ L B, Ershov F I
Vestn Ross Akad Med Nauk. 2004(2):29-34.
The paper contains an analysis of research on designing drugs based on acridine derivatives. The discussed series of compounds is of essential value since acridines belong to the group of natural compounds with the pronounced antibacterial and anti-tumor activity. Improved chemical-synthesis techniques made it possible to synthesize both simple and complex compounds of the acridine series; they displayed a clear pharmacological activity as anti-proliferative, anti-tumor and antiparasitic preparations. The ability to induce interferons (INF), type 1, is an expected property of simple acridine derivatives. A variety of INF inducers, now used clinically, have been designed recently on the basis of the above compounds. The most well-known acridine derivatives, their pharmacological properties, action mechanisms and outlooks for practical application are described in the paper. The unique qualities of acridines are primarily attractive due to the possibility of using them for the purpose-oriented designing of drugs. Thus, acridines were used as a basis to create the specific regulatory HIV-1 elements, proliferation inhibitors of leukemia cells and new anti-tumor drugs. The elaboration of complexes of acridines derivatives combined with peptides intercalating specifically into the DNA big or small grooves is the most outstanding trend of acridines' research--it opens up prospects for using them in the synthesis of compounds regulating the gene expression.
本文对基于吖啶衍生物设计药物的研究进行了分析。所讨论的这一系列化合物具有重要价值,因为吖啶属于具有显著抗菌和抗肿瘤活性的天然化合物类别。改进的化学合成技术使得合成吖啶系列的简单和复杂化合物成为可能;它们作为抗增殖、抗肿瘤和抗寄生虫制剂表现出明显的药理活性。诱导1型干扰素(INF)的能力是简单吖啶衍生物的一个预期特性。目前临床上使用的多种INF诱导剂最近都是基于上述化合物设计的。本文描述了最著名的吖啶衍生物、它们的药理特性、作用机制以及实际应用前景。吖啶的独特性质主要因其可用于有针对性的药物设计而具有吸引力。因此,吖啶被用作创建特定的HIV - 1调节元件、白血病细胞增殖抑制剂和新型抗肿瘤药物的基础。将吖啶衍生物与能特异性插入DNA大沟或小沟的肽结合形成复合物的研究是吖啶研究中最突出的趋势——这为其在合成调节基因表达的化合物方面开辟了前景。