Walsh T J, Giri N
Immunocompromised Host Section, National Cancer Institute, Bethesda, Maryland 20892, USA.
Eur J Clin Microbiol Infect Dis. 1997 Jan;16(1):93-7. doi: 10.1007/BF01575126.
Pradimicins are a new class of antifungal compounds currently undergoing preclinical and early phase I clinical trials. The pradimicin structure is characterized by an aglycone of dihydrobenzo (alpha) naphthacenequinone with substitutions by a D-amino acid and hexose sugar. Pradimicins possess a novel mechanism of action consisting of a specific binding recognition to terminal D-mannosides of the cell wall of Candida albicans, resulting in the formation of a ternary complex consisting of D-mannoside, pradimicin, and calcium that leads to disruption of the integrity of the fungal cell membrane. Pradimicin in the form of BMS-181184 has broad-spectrum in vitro antifungal activity against Candida spp., Cryptococcus neoformans, Aspergillus spp., dematiaceous molds, and the Zygomycetes. Fusarium spp. are comparatively resistant to high concentrations of pradimicin. Initial vivo studies indicate that pradimicins have antifungal activity against experimental murine disseminated candidiasis and disseminated aspergillosis. Early studies indicate an excellent therapeutic index with no major end-organ toxicity. Pradimicins warrant further investigation for treatment of opportunistic mycoses in immuno-compromised hosts.
制霉霉素是一类新型抗真菌化合物，目前正处于临床前和早期I期临床试验阶段。制霉霉素的结构特征是二氢苯并（α）萘并蒽醌苷元被一个D-氨基酸和己糖取代。制霉霉素具有一种新的作用机制，包括与白色念珠菌细胞壁末端D-甘露糖苷特异性结合识别，导致形成由D-甘露糖苷、制霉霉素和钙组成的三元复合物，从而破坏真菌细胞膜的完整性。以BMS-181184形式存在的制霉霉素对念珠菌属、新型隐球菌、曲霉属、暗色霉菌和接合菌具有广谱体外抗真菌活性。镰刀菌属对高浓度制霉霉素相对耐药。初步的体内研究表明，制霉霉素对实验性小鼠播散性念珠菌病和播散性曲霉病具有抗真菌活性。早期研究表明其治疗指数良好，无主要终末器官毒性。制霉霉素值得进一步研究用于治疗免疫功能低下宿主的机会性真菌病。
