Heredero-Bermejo Irene, Gómez-Casanova Natalia, Quintana Sara, Soliveri Juan, de la Mata Francisco Javier, Pérez-Serrano Jorge, Sánchez-Nieves Javier, Copa-Patiño José Luis
Department of Biomedicine and Biotechnology, Faculty of Pharmacy, University of Alcalá, 28871 Alcalá de Henares, Spain.
Department of Organic and Inorganic Chemistry, Research Institute in Chemistry "Andrés M. del Río" (IQAR), University of Alcalá, 28871 Alcalá de Henares, Spain.
Pharmaceutics. 2020 Sep 25;12(10):918. doi: 10.3390/pharmaceutics12100918.
spp. are one of the most common fungal pathogens. Biofilms formed by offer resistance mechanisms against most antifungal agents. Therefore, development of new molecules effective against these microorganisms, alone or in combination with antifungal drugs, is extremely necessary. In the present work, we carried out a screening process of different cationic carbosilane dendritic molecules against . In vitro activity against biofilm formation and biofilms was tested in both Colección Española de Cultivos Tipo (CECT) 1002 and clinical strains. Cytotoxicity was studied in human cell lines, and biofilm alterations were observed by scanning electron microscopy (SEM). Antifungal activity of the carbosilane dendritic molecules was assessed by monitoring cell viability using both established and novel cell viability assays. One out of 14 dendritic molecules tested, named BDSQ024, showed the highest activity with a minimum biofilm inhibitory concentration (MBIC) for biofilm formation and a minimum biofilm damaging concentration (MBDC) for existing biofilm of 16-32 and 16 mg/L, respectively. Synergy with amphotericin (AmB) and caspofungin (CSF) at non-cytotoxic concentrations was found. Therefore, dendritic compounds are exciting new antifungals effective at preventing biofilm formation and represent a potential novel therapeutic agent for treatment of infection in combination with existing clinical antifungals.
某些物种是最常见的真菌病原体之一。由它们形成的生物膜提供了针对大多数抗真菌剂的耐药机制。因此,开发单独或与抗真菌药物联合使用的对这些微生物有效的新分子极其必要。在本研究中,我们对不同的阳离子碳硅烷树枝状分子进行了针对某些物种的筛选过程。在西班牙典型培养物保藏中心(CECT)1002菌株和临床菌株中测试了其对生物膜形成和生物膜的体外活性。在人类细胞系中研究了细胞毒性,并通过扫描电子显微镜(SEM)观察了生物膜的变化。通过使用既定的和新颖的细胞活力测定法监测细胞活力来评估碳硅烷树枝状分子的抗真菌活性。在测试的14种树枝状分子中,有一种名为BDSQ024的分子表现出最高活性,其生物膜形成的最低生物膜抑制浓度(MBIC)和现有生物膜的最低生物膜破坏浓度(MBDC)分别为16 - 32 mg/L和16 mg/L。发现在非细胞毒性浓度下与两性霉素(AmB)和卡泊芬净(CSF)具有协同作用。因此,树枝状化合物是令人兴奋的新型抗真菌剂,可有效预防某些物种生物膜的形成,并代表了一种与现有临床抗真菌剂联合用于治疗某些物种感染的潜在新型治疗剂。