Elucidating antibacterial activity of heteroleptic triarylbismuthanes and synthesis of amide derivatives through activated ester intermediate

Abstract

Novel heteroleptic triarylbismuthane amides of Ar12Ar2Bi formula where Ar2 contains an amide functional group were tested for antimicrobial activity against various bacterial isolates: S. aureus, methicillin-resistant S. aureus (MRSA), S. pyogenes, E. faecalis and E. coli. The amides were prepared from synthetic intermediate B featuring an N-hydroxysuccinimide ester. The strategy behind B represents a departure from the more common approach of preparing triarylbismuthanes by direct arylation, thus avoiding the risk of dismutation when forming carbon-bismuth bond. Dismutation is essentially a scrambling process, a complication that yields a statistical distribution of heteroleptic and homoleptic products. The amides were prepared in modest to excellent yields (34–95%) and characterized by NMR and mass spectrometry. For antimicrobial testing in this study, additional heteroleptic triarylbismuthanes were included. Although no activity was evident for Gram-negative organisms, several triarylbismuthanes demonstrated significant antimicrobial activity against Gram-positive bacteria, including MRSA, while showing acceptable cytotoxicity profiles in mammalian cells. Presented data suggests that this class of compounds may possess acceptable characteristics to develop antimicrobial therapeutics in the future.

Keywords

• Heteroleptic
• Triarylbismuthane
• Organobismuth
• Activated ester
• Synthetic intermediate
• Antimicrobial activity