Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
J Mycol Med. 2018 Jun;28(2):314-319. doi: 10.1016/j.mycmed.2018.03.004. Epub 2018 Mar 26.
Candida albicans is the most important fungal pathogen that causes infections in humans, and the search for new therapeutic strategies for its treatment is essential.
The aim of this study was to evaluate the activity of seven naphthoquinones (β-lapachone, β-nor-lapachone, bromide-β-lapachone, hydroxy-β-lapachone, α-lapachone, α-nor-lapachone and α-xyloidone) on the growth of a fluconazole-resistant C. albicans oral clinical isolate and the effects of these compounds on the viability of mammalian cells, on yeast's morphogenesis, biofilm formation and cell wall mannoproteins availability.
All the compounds were able to completely inhibit the yeast growth. β-lapachone and α-nor-lapachone were the less cytotoxic compounds against L929 and RAW 264.7 cells. At IC, β-lapachone inhibited morphogenesis in 92%, while the treatment of yeast cells with α-nor-lapachone decreased yeast-to-hyphae transition in 42%. At 50μg/ml, β-lapachone inhibited biofilm formation by 84%, whereas α-nor-lapachone reduced biofilm formation by 64%. The treatment of yeast cells with β-lapachone decreased cell wall mannoproteins availability in 28.5%, while α-nor-lapachone was not able to interfere on this virulence factor. Taken together, data show that β-lapachone and α-nor-lapachone exhibited in vitro cytotoxicity against a fluconazole-resistant C. albicans strain, thus demonstrating to be promising candidates to be used in the treatment of infections caused by this fungus.
白色念珠菌是最重要的真菌病原体，可导致人类感染，因此寻找新的治疗策略至关重要。
本研究旨在评估七种萘醌（β-拉帕醌、β-去甲拉帕醌、溴代-β-拉帕醌、羟基-β-拉帕醌、α-拉帕醌、α-去甲拉帕醌和α-扁柏酮）对氟康唑耐药白色念珠菌口腔临床分离株生长的活性，以及这些化合物对哺乳动物细胞活力、酵母形态发生、生物膜形成和细胞壁甘露糖蛋白可用性的影响。
所有化合物均能完全抑制酵母生长。β-拉帕醌和α-去甲拉帕醌对 L929 和 RAW 264.7 细胞的细胞毒性最小。在 IC 时，β-拉帕醌抑制形态发生达 92%，而用α-去甲拉帕酮处理酵母细胞则使酵母到菌丝的过渡减少 42%。在 50μg/ml 时，β-拉帕醌抑制生物膜形成 84%，而α-去甲拉帕酮抑制生物膜形成 64%。用β-拉帕醌处理酵母细胞使细胞壁甘露糖蛋白的可用性降低 28.5%，而α-去甲拉帕酮则不能干扰这种毒力因子。综上所述，数据表明β-拉帕醌和α-去甲拉帕醌对氟康唑耐药白色念珠菌株具有体外细胞毒性，因此有望成为治疗该真菌引起的感染的候选药物。
