Activity of Antifungal Organobismuth(III) Compounds Derived from Alkyl Aryl Ketones against S. cerevisiae: Comparison with a Heterocyclic Bismuth Scaffold Consisting of a Diphenyl Sulfone

作者：Murafuji Toshihiro^*; Tomura Mai; Ishiguro Katsuya; Miyakawa Isamu

来源：Molecules, 2014, 19(8): 11077-11095.

DOI：10.3390/molecules190811077

• bismuth
• Lewis acidity
• hypervalent
• S. cerevisiae
• antifungal activity
• acetophenone

A series of hypervalent organobismuth(III) compounds derived from alkyl aryl ketones [XBi(5-R%26apos;C6H3-2-COR)(Ar)] was synthesized to investigate the effect of the compounds%26apos; structural features on their antifungal activity against the yeast Saccharomyces cerevisiae. In contrast to bismuth heterocycles [XBi(5-RC6H3-2-SO2C6H4-1%26apos;-)] derived from diphenyl sulfones, a systematic quantitative structure-activity relationship study was possible. The activity depended on the Ar group and increased for heavier X atoms, whereas lengthening the alkyl chain (R) or introducing a substituent (R%26apos;) reduced the activity. IBi(C6H4-2-COCH3)(4-FC6H4) was the most active. Its activity was superior to that of the related acyclic analogues ClBi[C6H4-2-CH2N(CH3)(2)](Ar) and ClBi(C6H4-2-SO2 tert-Bu)(Ar) and also comparable to that of heterocyclic ClBi(C6H4-2-SO2C6H4-1%26apos;-), which was the most active compound in our previous studies. Density function theory calculations suggested that hypervalent bismuthanes undergo nucleophilic addition with a biomolecule at the bismuth atom to give an intermediate ate complex. For higher antifungal activity, adjusting the lipophilicity-hydrophilicity balance, modeling the three-dimensional molecular structure around the bismuth atom, and stabilizing the ate complex appear to be more important than tuning the Lewis acidity at the bismuth atom.

• 出版日期2014-8