Department of Mycology, Pasteur Institute of Iran, Tehran, Iran.
Hematology and Oncology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Chem Biol Drug Des. 2019 May;93(5):949-959. doi: 10.1111/cbdd.13500. Epub 2019 Mar 13.
The antimicrobial activities of natural products have attracted much attention due to the increasing incidence of pathogens that have become resistant to drugs. Thus, it has been attempted to promisingly manage infectious diseases via a new group of therapeutic agents called antimicrobial peptides. In this study, a novel antifungal peptide, MCh-AMP1, was purified by reverse phase HPLC and sequenced by de novo sequencing and Edman degradation. The antifungal activity, safety, thermal, and pH stability of MCh-AMP1 were determined. This peptide demonstrated an antifungal activity against the tested Candida and Aspergillus species with MIC values in the range of 3.33-6.66 μM and 6.66-13.32 μM, respectively. Further, physicochemical properties and molecular modeling of MCh-AMP1 were evaluated. MCh-AMP1 demonstrated 3.65% hemolytic activity at the concentration of 13.32 μM on human red blood cells and 10% toxicity after 48 hr at the same concentration on HEK293 cell lines. The antifungal activity of MCh-AMP1 against Candida albicans was stable at a temperature range of 30-50°C and at the pH level of 7-11. The present study indicates that MCh-AMP1 may be considered as a new antifungal agent with therapeutic potential against major human pathogenic fungi.
由于对抗生素产生耐药性的病原体的发病率不断增加,天然产物的抗菌活性引起了广泛关注。因此,人们试图通过一类新的治疗药物——抗菌肽来有效地治疗感染性疾病。在这项研究中,通过反相 HPLC 对一种新型抗真菌肽 MCh-AMP1 进行了纯化,并通过从头测序和 Edman 降解进行了测序。测定了 MCh-AMP1 的抗真菌活性、安全性、热稳定性和 pH 稳定性。该肽对测试的念珠菌和曲霉菌具有抗真菌活性,MIC 值分别为 3.33-6.66 μM 和 6.66-13.32 μM。此外,还评估了 MCh-AMP1 的物理化学性质和分子建模。MCh-AMP1 在 13.32 μM 的浓度下对人红细胞的溶血活性为 3.65%,在相同浓度下对 HEK293 细胞系的毒性为 10%,作用 48 小时后。MCh-AMP1 对白色念珠菌的抗真菌活性在 30-50°C 的温度范围内和 7-11 的 pH 水平下稳定。本研究表明,MCh-AMP1 可被视为一种具有治疗潜力的新型抗真菌药物,可用于治疗主要的人类致病性真菌。