Xisto Mariana Ingrid Dutra da Silva, Rollin-Pinheiro Rodrigo, de Castro-Almeida Yuri, Dos Santos-Freitas Giulia Maria Pires, Rochetti Victor Pereira, Borba-Santos Luana Pereira, da Silva Fontes Yasmin, Ferreira-Pereira Antonio, Rozental Sonia, Barreto-Bergter Eliana
Laboratório de Química Biológica de Microrganismos, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
Laboratório de Biologia Celular de Fungos, Programa de Biologia Celular e Parasitologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
J Fungi (Basel). 2023 Jan 31;9(2):187. doi: 10.3390/jof9020187.
Mucormycosis is considered concerning invasive fungal infections due to its high mortality rates, difficult diagnosis and limited treatment approaches. Mucorales species are highly resistant to many antifungal agents and the search for alternatives is an urgent need. In the present study, a library with 400 compounds called the Pandemic Response Box was used and four compounds were identified: alexidine and three non-commercial molecules. These compounds showed anti-biofilm activity, as well as alterations in fungal morphology and cell wall and plasma membrane structure. They also induced oxidative stress and mitochondrial membrane depolarization. In silico analysis revealed promising pharmacological parameters. These results suggest that these four compounds are potent candidates to be considered in future studies for the development of new approaches to treat mucormycosis.
毛霉菌病因其高死亡率、诊断困难和治疗方法有限，被视为令人担忧的侵袭性真菌感染。毛霉目真菌对许多抗真菌药物具有高度抗性，因此迫切需要寻找替代药物。在本研究中，使用了一个包含400种化合物的文库，称为大流行应对盒，并鉴定出四种化合物：氯己定和三种非商业分子。这些化合物表现出抗生物膜活性，以及真菌形态、细胞壁和质膜结构的改变。它们还诱导氧化应激和线粒体膜去极化。计算机分析显示出有前景的药理学参数。这些结果表明，这四种化合物是未来开发治疗毛霉菌病新方法研究中值得考虑的有力候选药物。
