Investigating the antimicrobial activity, cytotoxicity, and action mechanism of acylated and amidated derivatives of AurH1 antifungal peptide

• Published in: BMC microbiology 2023-11, Vol.23 (1), p.1-332, Article 332
• Main Authors: Nikookar Golestani, Reyhane, Ghods, Elahe, Rostamian, Mosayeb, Madanchi, Hamid, Talebi, Ahmad Farhad
• Format: Article
• Language: English
• Subjects: Acylation; Amidation; Antibiotics; Anticancer properties; Antifungal activity; Antifungal agents; Antifungal peptides; Antimicrobial activity; Antimicrobial agents; Antimicrobial peptides; Antitumor activity; Aurein1.2; AurH1; Bacteria; Breast cancer; Cell death; Cells; COVID-19; Cytotoxicity; Drug resistance; Drug resistance in microorganisms; Fibroblasts; Fungal infections; Fungi; Fungicides; Immune system; Investigations; Microbiological research; Microorganisms; Penicillin; Peptides; Synthesis; Testing; Toxicity
• ISSN: 1471-2180; 1471-2180
• DOI: 10.1186/s12866-023-03090-7

The increasing growth of microbial resistance threatens the health of human societies. Therefore, the discovery and design of new antibiotics seem necessary. Today, antimicrobial peptides (AMPs) are receiving attention due to their unique properties. In our previous studies, exclusive antifungal effects of AurH1, which is a truncated and modified form of Aurein1.2, were synthesized. In this study, AurH1 antifungal peptide was synthesized into acylated (Ac-AurH1) and amidated (AurH1-NH.sub.2) derivatives, and their antifungal activity, cytotoxicity, anticancer activity, hemolytic effects were investigated. Finally, the time- of killing, the action mechanism of amidated and acylated peptides, and the effects of salts and human serum on their antimicrobial potency were determined. All the results obtained about these peptides were compared with the AurH1 without chemical modifications. The results showed that amidation at the C-terminal of AurH1 compared to acylation at the N-terminal of it can improve the antifungal properties and cytotoxicity of AurH1. The results showed that AurH1 amidation can maintain the antifungal activity of this peptide in the culture medium containing specific dilutions of human serum compared to the intact AurH1. Also, the amidation of the C-terminal of AurH1 could not affect the mechanism of action and its time -of killing. As a result, the amidation of the C-terminal of the AurH1 is a suitable strategy to improve its antifungal properties and cytotoxicity. This modification can enhance its properties for animal studies.