Coelho Rowena Alves, Figueiredo-Carvalho Maria Helena Galdino, Almeida-Silva Fernando, de Souza Rabello Vanessa Brito, de Souza Gabriela Rodrigues, Sangenito Leandro Stefano, Joffe Luna Sobrino, Santos André Luis Souza Dos, da Silva Lourenço Maria Cristina, Rodrigues Marcio L, Almeida-Paes Rodrigo
Laboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, INI/Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil.
Plataforma de Bioensaios RPT 11B, Instituto Nacional de Infectologia Evandro Chagas, INI/Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil.
J Fungi (Basel). 2023 Jul 16;9(7):753. doi: 10.3390/jof9070753.
Chromoblastomycosis (CBM) is a neglected human implantation mycosis caused by several dematiaceous fungal species. Currently available therapy is usually associated with physical methods, especially surgery, and with high refractoriness. Therefore, drug discovery for CBM is essential. Drug repositioning is a strategy used to facilitate the discovery of new treatments for several diseases. The aim of this study was to discover substances with antifungal activity against CBM agents from a collection of drugs previously approved for use in human diseases. A screening was performed with the NIH Clinical Collection against . Ten substances, with clinical applicability in CBM, inhibited fungal growth by at least 60%. The minimum inhibitory concentration (MIC) of these substances was determined against other CBM agents, and the benzimidazoles albendazole, mebendazole and thiabendazole presented the lowest MIC values. The selectivity index, based on MIC and cytotoxicity of these substances, revealed albendazole to be more selective. To investigate a possible synergism of this benzimidazole with itraconazole and terbinafine, the chequerboard method was used. All interactions were classified as indifferent. Our current results suggest that benzimidazoles have repositioning potential against CBM agents. Albendazole seems to be the most promising, since it presented the highest selectivity against all dematiaceous fungi tested.
着色芽生菌病（CBM）是一种由多种暗色真菌引起的被忽视的人类植入性真菌病。目前可用的治疗方法通常与物理方法相关，尤其是手术，且难治性高。因此，针对CBM的药物研发至关重要。药物重新定位是一种用于促进多种疾病新疗法发现的策略。本研究的目的是从先前已批准用于人类疾病的药物库中发现对CBM病原体具有抗真菌活性的物质。使用美国国立卫生研究院临床药物库对……进行了筛选。十种对CBM具有临床适用性的物质抑制真菌生长至少60%。测定了这些物质对其他CBM病原体的最低抑菌浓度（MIC），苯并咪唑类的阿苯达唑、甲苯达唑和噻苯达唑的MIC值最低。基于这些物质的MIC和细胞毒性的选择性指数显示阿苯达唑更具选择性。为了研究这种苯并咪唑与伊曲康唑和特比萘芬可能的协同作用，采用了棋盘法。所有相互作用均被归类为无作用。我们目前的结果表明苯并咪唑类对CBM病原体具有重新定位的潜力。阿苯达唑似乎最有前景，因为它对所有测试的暗色真菌表现出最高的选择性。
