Sulfur-containing ferrocenyl alcohols and oximes: new promising antistaphylococcal agents.

A small library containing four different series of new ferrocene derivatives, 2-(alkylsulfanyl)-1-ferrocenylethan-1-ols, 3-(alkylsulfanyl)-1-ferrocenylpropan-1-ols, (E)- and (Z)-2-(alkylsulfanyl)-1-ferrocenylethan-1-one oximes, and (E)- and (Z)-3-(alkylsulfanyl)-1-ferrocenylpropan-1-one oximes (36 different compounds in total) was synthesized starting from ferrocene and the corresponding sulfanyl acids. All compounds were spectrally (IR and NMR) and electrochemically characterized. In general, the obtained compounds were found to exhibit very strong antimicrobial activities (broth microdilution assay) against the tested microorganisms (six common human pathogens). For the majority of the tested compounds, the determined MIC values were either under the 10 μg/ml MIC limit recognized to delimit efficient antimicrobials or were comparable to/lower than those of the used positive controls (tetracycline/nystatin). The most susceptible organism was found to be Staphylococcus aureus with MIC values even reaching 0.001 μg/ml. The presence of -CH(OH)(CH(2))(n)S- and -CH(=NOH)(CH(2))(n)S- (n=1 or 2) structural fragments seems to be essential for the observed strong activity (introduction of hydroxyimino and alcohol functionalities, instead of the keto function, resulted in a more than 10(5)-fold increase in antistaphylococcal activity in some instances). Nevertheless, a possible influence of the ferrocenyl-core redox chemistry (Fe(2+)/Fe(3+)) should not be disregarded. The studied alcohols exhibited a reversible one-electron redox couple at almost the same position as ferrocene, while the hydroxyimino group conjugated with cyclopentadienyl ring considerably shifted the redox potential of the ferrocene unit in oximes.