Laboratório de Biologia Celular de Fungos; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, United States.
Curr Pharm Des. 2020;26(14):1524-1531. doi: 10.2174/1381612826666200217120321.
Onychomycosis is a chronic nail infection caused by fungi frequently resistant to antifungal treatments. Recalcitrance in nail infections is a result of reduced antifungal penetration due to biofilm formation, combined with poor patient compliance with the treatment, which can be as long as 18 months.
Metal-drug complexation is a widely used strategy to increase drug efficacy. Therefore, the aim of this work was to evaluate the antifungal and anti-biofilm activity of several metal-azole complexes against Candida albicans and Candida glabrata.
Susceptibility assays and scanning electron microscopy were performed to determine the anti-biofilm activity of eight metal-azole complexes in vitro and ex-vivo, using human nail fragments.
In vitro susceptibility assays showed that complexation of both Au(I) and Zn(II) to clotrimazole and ketoconazole improved the anti-biofilm activity compared to the azole alone. Using an ex-vivo model of biofilm formation on fragments of human nails, we also demonstrate the improved efficacy of metal-azole complexes against biofilms of C. albicans and C. glabrata that resembles the onychomycosis structure. Noteworthy, biofilms of C. glabrata were more susceptible to the optimized complexes than those of C. albicans.
In conclusion, metal-azole complexes used in this work show promising anti-biofilm activity and further clinical studies should confirm its potential for the treatment of Candida-associated onychomycosis.
甲真菌病是一种由真菌引起的慢性指甲感染，这些真菌通常对抗真菌治疗有耐药性。指甲感染的顽固性是由于生物膜形成导致抗真菌药物渗透减少，再加上患者对治疗的依从性差（治疗时间可能长达 18 个月）所致。
金属-药物络合是一种提高药物疗效的常用策略。因此，本研究旨在评估几种金属-唑类配合物对白色念珠菌和光滑念珠菌的抗真菌和抗生物膜活性。
通过体外和离体人指甲碎片，进行药敏试验和扫描电子显微镜检查，以确定 8 种金属-唑类配合物的抗生物膜活性。
体外药敏试验表明，金（I）和锌（II）与克霉唑和酮康唑络合后，与唑类药物单独使用相比，抗生物膜活性得到提高。使用人指甲碎片生物膜形成的离体模型，我们还证明了金属-唑类配合物对白色念珠菌和光滑念珠菌生物膜的疗效得到改善，这类似于甲真菌病的结构。值得注意的是，与白色念珠菌相比，优化后的配合物对光滑念珠菌生物膜的敏感性更高。
综上所述，本研究中使用的金属-唑类配合物显示出有希望的抗生物膜活性，进一步的临床研究应证实其治疗与念珠菌相关的甲真菌病的潜力。
