Impaired ergosterol biosynthesis mediated fungicidal activity of oil based tin polymer

摘要

Candida represents an important group of opportunistic fungal pathogens which causes infections in immunocompromised patients. The increasing emergence of fungal resistance to currently available antimycotic agents, especially azoles is a major problem. A vegetable-based organotin polymer synthesised by the condensation of fatty amide diol (N, N 1-bis 2 hydroxy ethyl castor oil fatty amide) and butyl tin chloride dihydroxide has been reported to posses antimicrobial activity. This study is an attempt to investigate the antifungal activity of this compound against several fluconazole-susceptible and resistant clinical Candida isolates and to understand its mode of action. The susceptibility tests for the polymer were carried out in terms of minimum inhibitory concentrations (MICs) and disc diffusion assays against fifty-nine Candida isolates by employing standard protocols. The ergosterol-mediated antifungal activity was analysed by the sterol quantitation method. The organotin polymer was found to be effective, to varying extent, against all the Candida isolates including the resistant ones. It showed a low MIC value, which was fungicidal in contrast to the fungistatic fluconazole and caused considerable impairment of ergosterol biosynthesis in all the strains tested. This compound may be targeting the ergosterol biosynthesis pathway and may be used as an alternative to fluconazole which develops resistance during therapy. The selectively fungicidal characteristics of the organotin polymer indicate that this compound might be a promising antifungal agent.