Salama Ali, Almaaytah Ammar, Darwish Rula M
Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, University of Jordan, Amman 11942, Jordan.
Department of Pharmacy, Faculty of Pharmacy, Middle East University, Amman 11831, Jordan.
Antibiotics (Basel). 2021 Jun 13;10(6):712. doi: 10.3390/antibiotics10060712.
(1) Background: Antimicrobial resistance represents an urgent health dilemma facing the global human population. The development of novel antimicrobial agents is needed to face the rising number of resistant bacteria. Ultrashort antimicrobial peptides (USAMPs) are considered promising antimicrobial agents that meet the required criteria of novel antimicrobial drug development. (2) Methods: Alapropoginine was rationally designed by incorporating arginine (R), biphenylalanine (B), and naproxen to create an ultrashort hexapeptide. The antimicrobial activity of alapropoginine was evaluated against different strains of bacteria. The hemolytic activity of alapropoginine was also investigated against human erythrocytes. Finally, synergistic studies with antibiotics were performed using the checkerboard technique and the determination of the fractional inhibitory index. (3) Results: Alapropoginine displayed potent antimicrobial activities against reference and multi-drug-resistant bacteria with MIC values of as low as 28.6 µg/mL against methicillin-resistant S. aureus. Alapropoginine caused negligible toxicity toward human red blood cells. Moreover, the synergistic studies showed improved activities for the combined conventional antibiotics with a huge reduction in their antimicrobial concentrations. (4) Conclusions: The present study indicates that alapropoginine exhibits promising antimicrobial activity against reference and resistant strains of bacteria with negligible hemolytic activity. Additionally, the peptide displays synergistic or additive effects when combined with several antibiotics.
(1) 背景：抗菌药物耐药性是全球人类面临的紧迫健康难题。面对耐药细菌数量的不断增加，需要开发新型抗菌药物。超短抗菌肽（USAMPs）被认为是符合新型抗菌药物开发所需标准的有前景的抗菌剂。(2) 方法：通过掺入精氨酸（R）、联苯丙氨酸（B）和萘普生合理设计了阿拉普罗吉宁，以创建一种超短六肽。评估了阿拉普罗吉宁对不同细菌菌株的抗菌活性。还研究了阿拉普罗吉宁对人红细胞的溶血活性。最后，使用棋盘法和分数抑制指数测定法进行了与抗生素的协同研究。(3) 结果：阿拉普罗吉宁对参考菌株和多重耐药细菌显示出强大的抗菌活性，对耐甲氧西林金黄色葡萄球菌的最低抑菌浓度（MIC）值低至28.6 µg/mL。阿拉普罗吉宁对人红细胞的毒性可忽略不计。此外，协同研究表明，联合使用传统抗生素时活性增强，且抗菌浓度大幅降低。(4) 结论：本研究表明，阿拉普罗吉宁对参考菌株和耐药菌株显示出有前景的抗菌活性，溶血活性可忽略不计。此外，该肽与几种抗生素联合使用时显示出协同或相加作用。
