Instituto de Pesquisa e Desenvolvimento - IP&D, Universidade do Vale do Paraíba - UNIVAP, Av. Shishima Hifumi, São José dos Campos, SP 2911, Brazil.
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, Brazil.
J Trace Elem Med Biol. 2022 Sep;73:127019. doi: 10.1016/j.jtemb.2022.127019. Epub 2022 Jun 10.
Systemic candidiasis is produced by Candida albicans or non-albicans Candida species, opportunistic fungi that produce both superficial and invasive infections. Despite the availability of a wide range of antifungal agents for the treatment of candidiasis, failure of therapy is observed frequently, which opens new avenues in the field of alternative therapeutic strategies.
The effects of p,p'-methoxyl-diphenyl diselenide [(MeOPhSe)], a synthetic organic selenium (organochalcogen) compound, were investigated on virulence factors of C. krusei and compared with its antifungal effects on the virulence factors related to adhesion to cervical epithelial cell surfaces with C. albicans.
(MeOPhSe), a compound non-toxic in epithelial (HeLa) and fibroblastic (Vero) cells, inhibited the growth in a dose-dependent manner and changed the kinetics parameters of C. krusei and, most importantly, extending the duration of lag phase of growth, inhibiting biofilm formation, and changing the structure of biofilm. Also, (MeOPhSe) reduced C. albicans and C. krusei adherence to cervical epithelial cells, an important factor for the early stage of the Candida-host interaction. The reduction was 37.24 ± 2.7 % in C. krusei (p = 0.00153) and 32.84 ± 3.2 % in C. albicans (p = 0.0072) at 20 µM (MeOPhSe), and the effect is in a concentration-dependent manner. Surprisingly, the antifungal potential on adhesion was similar between both species, indicating the potential of (MeOPhSe) as a promising antifungal drug against different Candida infections.
Overall, we demonstrated the potential of (MeOPhSe) as an effective antifungal drug against the virulence factors of Candida species.
系统性念珠菌病是由白念珠菌或非白念珠菌念珠菌属引起的，这些机会性真菌可引起浅表和侵袭性感染。尽管有多种抗真菌药物可用于治疗念珠菌病，但治疗失败的情况经常发生，这为替代治疗策略开辟了新的途径。
研究了合成有机硒（有机硫属元素）化合物 p,p'-甲氧基二苯二硒醚 [(MeOPhSe)] 对克柔念珠菌毒力因子的影响，并将其与抗真菌作用进行了比较与白念珠菌与宫颈上皮细胞表面黏附相关的毒力因子。
（MeOPhSe）在上皮（HeLa）和成纤维细胞（Vero）细胞中无毒性，以剂量依赖性方式抑制生长，并改变克柔念珠菌的动力学参数，最重要的是，延长生长迟滞期，抑制生物膜形成，并改变生物膜结构。此外，（MeOPhSe）降低了 C. albicans 和 C. krusei 对宫颈上皮细胞的黏附，这是念珠菌与宿主相互作用早期的一个重要因素。在 20 µM（MeOPhSe）时，C. krusei 的减少率为 37.24±2.7%（p=0.00153），C. albicans 的减少率为 32.84±3.2%（p=0.0072），这种减少呈浓度依赖性。令人惊讶的是，两种真菌在黏附方面的抗真菌潜力相似，表明（MeOPhSe）作为一种有前途的抗真菌药物，可能对抗不同的念珠菌感染。
总的来说，我们证明了（MeOPhSe）作为一种有效的抗真菌药物，具有针对念珠菌属毒力因子的潜力。
