BMVC衍生物對於念珠菌的殺菌效果

Abstract

近年來伺機性真菌對於免疫不全患者致病性增加，已成為醫院院內感染主要感染病源，而目前常用的抗真菌藥物，有些副作用過強、有些則是易使菌產生抗藥性，例如Fluconazole，導致治療效果降低，因此開發新型之藥物有其必要性。 本研究發現3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide (BMVC)之衍生物9個與12個長碳鏈(BMVC-9C、BMVC-12C)對於念珠菌屬具有殺菌效果，並由藥物敏感性測試實驗結果得知BMVC-12C對標準念珠菌菌株與臨床的抗藥性菌株Candida krusei、Candida glabrata與Candida tropicalis具有類似殺菌效果。 透過共軛焦顯微鏡觀察結果，BMVC的衍生物中較不具殺菌效果的BMVC-4C、BMVC-8C，與BMVC一樣主要是存在細胞核。而BMVC-9C及BMVC-12C具殺菌效果的BMVC衍生物則會進入念珠菌的粒線體。因此推測這兩個衍生物殺菌機制，可能與粒線體功能的破壞相關。故本研究發現BMVC-12C具有潛力發展成抗真菌藥物。

In recent years, infection of opportunistic pathogenic fungus has increased in patients with immunodeficiency, which has become the main source of nosocomial infection. Presently, antifungal drugs have been used to treat the infection but side effects as well as drug resistance become serious issues. Therefore the development of new drugs is necessary. In this study, we found that 3,6-bis (1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC) derivatives, BMVC-9C and BMVC-12C, have the antifungal effect against Candida species. Using drug susceptibility test, BMVC-12C shows antifungal effect against standard Candida strains and clinical drug-resistant strains of Candida krusei, Candida glabrata and Candida tropicalis. Under confocal microscopy analysis, BMVC derivatives (BMVC, BMVC-4C, BMVC-8C) which have no antifungal effect localize in the nucleus of Candida. BMVC-9C and BMVC-12C which have antifungal effect were found to localize in the mitochondria of Candida. Our results indicate that the antifungal mechanism of BMVC-9C and BMVC-12C might relate to the destruction of mitochondrial function suggesting the potential of BMVC-12C as an antifungal agent.