Institute of Organic Chemistry PAS, Kasprzaka 44/52, 01-224 Warsaw, Poland.
Department of Animal Nutrition, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3, 05-110 Jabłonna, Poland.
Molecules. 2022 Jun 6;27(11):3633. doi: 10.3390/molecules27113633.
An efficient method for the synthesis of functionalized peptidomimetics via multicomponent Ugi reaction has been developed. The application of trifluoroethanol (TFE) as a reaction medium provided desired products with good yields. Further, using the developed cyclisation reaction, the obtained peptidomimetics were transformed into the cyclic analogues (diketopiperazines, DKPs). The goal of the performed studies was to revised and compare whether the structure of the obtained structurally flexible acyclic peptidomimetics and their rigid cycling analogue DKPs affect antimicrobial activity. We studied the potential of synthesized peptidomimetics, both cyclic and acyclic, as antimicrobial drugs on model bacteria strains (k12, R2-R4). The biological assays reveal that DKPs hold more potential as antimicrobial drugs compared to open chain Ugi peptidomimetics. We believe that it can be due to the rigid cyclic structure of DKPs which promotes the membrane penetration in the cell of studied pathogens. The obtained data clearly indicate the high antibiotic potential of synthesized diketopiperazine derivatives over tested antibiotics.
已经开发出一种通过多组分 Ugi 反应合成功能化肽模拟物的有效方法。三氟乙醇 (TFE) 作为反应介质的应用提供了具有良好收率的所需产物。此外，使用开发的环化反应，将获得的肽模拟物转化为环状类似物（二酮哌嗪，DKP）。进行这些研究的目的是修改并比较所获得的结构灵活的非环状肽模拟物及其刚性环化类似物 DKP 的结构是否影响抗菌活性。我们研究了合成的肽模拟物（环状和非环状）作为模型细菌菌株（k12、R2-R4）的抗菌药物的潜力。生物测定表明，与开链 Ugi 肽模拟物相比，DKP 具有更大的作为抗菌药物的潜力。我们认为，这可能是由于 DKP 的刚性环状结构促进了研究病原体细胞中的膜穿透。所得数据清楚地表明，合成的二酮哌嗪衍生物具有比测试的抗生素更高的抗生素潜力。
