Institute of Oceanology, Polish Academy of Sciences, Powstańców Warszawy 55, PL-81712 Sopot, Poland.
Division of Marine Biotechnology, Institute of Oceanography, University of Gdańsk, M. J. Piłsudskiego 46, PL-81378 Gdynia, Poland.
Mar Drugs. 2022 Jan 21;20(2):93. doi: 10.3390/md20020093.
Aeruginosamides (AEGs) are classified as cyanobactins, ribosomally synthesized peptides with post-translational modifications. They have been identified in cyanobacteria of genera , , and . In this work, the new data on the in vitro activities of three AEG variants, AEG A, AEG625 and AEG657, and their interactions with metabolic enzymes are reported. Two aeruginosamides, AEG625 and AEG657, decreased the viability of human breast cancer cell line T47D, but neither of the peptides was active against human liver cancer cell line Huh7. AEGs also did not change the expression of MIR92b-3p, but for AEG625, the induction of oxidative stress was observed. In the presence of a liver S9 fraction containing microsomal and cytosolic enzymes, AEG625 and AEG657 showed high stability. In the same assays, quick removal of AEG A was recorded. The peptides had mild activity against three cytochrome P450 enzymes, CYP2C9, CYP2D6 and CYP3A4, but only at the highest concentration used in the study (60 µM). The properties of AEGs, i.e., cytotoxic activity and in vitro interactions with important metabolic enzymes, form a good basis for further studies on their pharmacological potential.
苍蓝酰胺（AEGs）被归类为蓝细菌素，是一类核糖体合成的具有翻译后修饰的肽类化合物。它们已在 、 和 属的蓝细菌中被鉴定出来。在这项工作中，报道了三种 AEG 变体（AEG A、AEG625 和 AEG657）的体外活性及其与代谢酶相互作用的新数据。两种苍蓝酰胺 AEG625 和 AEG657 降低了人乳腺癌细胞系 T47D 的活力，但这两种肽对人肝癌细胞系 Huh7 均无活性。AEGs 也没有改变 MIR92b-3p 的表达，但观察到 AEG625 诱导了氧化应激。在含有微粒体和胞质酶的肝脏 S9 部分存在的情况下，AEG625 和 AEG657 表现出很高的稳定性。在相同的测定中，记录到 AEG A 迅速被去除。这些肽对三种细胞色素 P450 酶 CYP2C9、CYP2D6 和 CYP3A4 具有温和的活性，但仅在研究中使用的最高浓度（60 µM）下才有活性。AEGs 的特性，即细胞毒性活性和与重要代谢酶的体外相互作用，为进一步研究其药理潜力奠定了良好的基础。
