Effect of diorganotin(IV) carboxylate complexes, [N-(2-carboxyphenyl) salicylideneiminato]dimethyltin(IV), bis(μ3-oxo)bis(μ-O-aminobenzoato-O,O') bis(O-aminobenzoato)tetrakis[dimethyltin(IV)] and bis(O-aminobenzoato-O,O) di-n-butyltin(IV), on the membrane of Candida albicans cells - a mechanistic investigation of the antifungal activity of organotin complexes.

摘要

The in vitro anti-fungal activity of diorganotin(V) carboxylate complexes, [N-(2-carboxyphenyl)salicylideneiminato] dimethyltin(IV) (1), bis(μ3-oxo)bis(μ-O-aminobenzoato-O,O')bis(O-aminobenzoato)tetrakis[dimethyltin(IV)] (2) and bis(O-aminobenzoato-O,O')di-n-butyltin(IV) (3) has been screened against Candida albicans. The complexes, prepared by minor modifications of a literature method, have been fully characterized. The biological activities of complexes 1 -3 on cultures of Candida albicans have been studied and the related mechanism has been investigated. No changes in DNA integrity or in the mitochondria function have been observed. However, all the tin compounds were found to reduce the ergosterol biosynthesis. The compounds have inhibitory concentrations (IC_(50)) in the range of 7.5-2O.O μg ml~(-1), with compound 3 the most active. These results were compared with those provided by the literature, using myconazole, amphotericin B and fluconazole as standards. Scanning electron microscopy and transmission electron microscopy of the cells treated with complexes 1-3, revealed severe damage on the C. albicans cells compromising the cellular integrity, suggesting that the organotin complexes act on the cell membrane, in view of cytoplasm leaking and cellular deformation. The data indicate for 1 -3 a mechanism of action similar to that of azole drugs, such as ketoconazole or fluconazole, normally used in Candida infections.