Ferreira Soraya Z, Carneiro Hellem C, Lara Hugo A, Alves Rosemeire B, Resende Jarbas M, Oliveira Heloísa M, Silva Luciana M, Santos Daniel A, Freitas Rossimiriam P
Departamento de Química, Instituto de Ciências Exatas, and Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil.
Serviço de Biologia Celular, Diretoria de Pesquisa e Desenvolvimento da Fundação Ezequiel Dias , Belo Horizonte, Brazil.
ACS Med Chem Lett. 2015 Jan 7;6(3):271-5. doi: 10.1021/ml500393q. eCollection 2015 Mar 12.
Antimicrobial peptides (AMPs) are currently being investigated as potential sources of novel therapeutics against an increasing number of microorganisms resistant to conventional antibiotics. The conjugation of an AMP to other bioactive compounds is an interesting approach for the development of new derivatives with increased antimicrobial efficiency and broader spectra of action. In this work, the synthesis of a new peptide-coumarin conjugate via copper(I)-catalyzed azide-alkyne cycloaddition is described. The conjugate was assayed for in vitro cytotoxicity and displayed antifungal activity against Cryptococcus gattii and Cryptococcus neoformans. Additionally, the conjugate exhibited increased antifungal efficacy when compared with the individual peptide, coumarin, or triazole moieties. Treatment of C. gattii with the peptide-coumarin conjugate enhanced the production of reactive oxygen species, suggesting that the oxidative burst plays an important role in the mechanism of action of the conjugate.
抗菌肽（AMPs）目前正作为新型治疗药物的潜在来源进行研究，以对抗越来越多对传统抗生素耐药的微生物。将抗菌肽与其他生物活性化合物偶联是开发具有更高抗菌效率和更广泛作用谱的新衍生物的一种有趣方法。在这项工作中，描述了通过铜（I）催化的叠氮化物-炔烃环加成反应合成一种新的肽-香豆素共轭物。对该共轭物进行了体外细胞毒性测定，并显示出对加氏隐球菌和新生隐球菌的抗真菌活性。此外，与单个肽、香豆素或三唑部分相比，该共轭物表现出更高的抗真菌效力。用肽-香豆素共轭物处理加氏隐球菌可增强活性氧的产生，这表明氧化爆发在该共轭物的作用机制中起重要作用。
