Angelova Nora, Iliev Ivan, Nemska Veronica, Dzimbova Tatyana, Georgieva Nelly, Danalev Dancho, Naydenova Emilia
Department of Organic Chemistry, University of Chemical Technology and Metallurgy, 1797 Sofia, Bulgaria.
Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Molecules. 2025 May 5;30(9):2050. doi: 10.3390/molecules30092050.
Extensive use of classical antibiotics has led to the growing emergence of many resistant strains of pathogenic bacteria. To combat this challenge, researchers have turned to the antimicrobial peptides (AMPs). Aurein 1.2 (GLFDIIKKIAESF-NH2) was demonstrated to have broad spectrum bi-functionality against bacterial and cancer cells. The Solid Phase Peptide Synthesis (Fmoc-strategy) was used for the synthesis of new analogs of aurein 1.2. The purity of all compounds was monitored by HPLC, and their structures were proven using mass spectrometry. Cytotoxicity and antiproliferative effects were studied using 3T3 NRU and MTT tests, respectively. The antibacterial activity was estimated against Gram-positive and Gram-negative bacteria using broth microdilution method in concentrations from 0 to 320 µg/mL to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). The antiproliferative activity test shows that the peptide analog EH [Orn] has the highest activity (IC = 44 ± 38 μM) for the three cell lines studied (MCF-12F, MCF-7, and MDA-MB-231). The same compound exhibited good antimicrobial activity. The obtained results reveal that replacement of Lys with non-proteinogenic amino acids can increase both the potency and activity spectra of natural template peptides, making them suitable candidates for new drug development.
经典抗生素的广泛使用导致了许多致病性细菌耐药菌株的不断出现。为应对这一挑战，研究人员将目光转向了抗菌肽（AMPs）。已证明奥瑞因1.2（GLFDIIKKIAESF-NH2）对细菌和癌细胞具有广谱双功能。采用固相肽合成法（Fmoc策略）合成了奥瑞因1.2的新类似物。所有化合物的纯度通过高效液相色谱法监测，其结构通过质谱法确证。分别使用3T3 NRU试验和MTT试验研究细胞毒性和抗增殖作用。采用肉汤微量稀释法在0至320μg/mL浓度下评估对革兰氏阳性菌和革兰氏阴性菌的抗菌活性，以确定最低抑菌浓度（MIC）和最低杀菌浓度（MBC）。抗增殖活性试验表明，肽类似物EH[Orn]对所研究的三种细胞系（MCF-12F、MCF-7和MDA-MB-231）具有最高活性（IC = 44±38μM）。同一化合物表现出良好的抗菌活性。所得结果表明，用非蛋白质氨基酸取代赖氨酸可以提高天然模板肽的效力和活性谱，使其成为新药开发的合适候选物。
