Germa-γ-lactones as novel inhibitors of bacterial urease activity

Organogermanium compounds have been used as pharmacological agents. However, very few reports are available on the synthesis and antibacterial activities of lactones containing organogermaniums. The purpose of the present investigation was to determine the effects of different lactone-substituted organogermaniums on bacterial growth and their urease activity. We report synthesis of 12 germa-γ-lactones (GeL) and their antimicrobial activities against several bacterial pathogens. Antibacterial action of all GeL was highly selective against Gram-negative bacilli, particularly Proteus mirabilis, an important pathogen infecting the urinary tract. Furthermore, our data indicate that 8-quinoline derivatives were more potent against P. mirabilis than 2-methyl-8-quinoline. For example, the β-(o-methylphenyl)-γ,γ-bis(8-quinolinoxy)germa-γ-lactone and β-(o-methoxyphenyl)-γ,γ-bis(8-quinolinoxy)germa-γ-lactone were maximally active with MIC90 of 61 and 94 μM, respectively. In vitro studies demonstrated a linear correlation between antibacterial activity and inhibition of P. mirabilis urease enzyme. Further kinetic analyses revealed that inhibition occurred in a noncompetitive and concentration-dependent manner with the minimum IC50 of 31 μM for β-(o-methoxyphenyl)-γ,γ-bis(8-quinolinoxy)germa-γ-lactone. In conclusion, these findings suggest that GeL have potential to be developed as antimicrobial agents against P. mirabilis infection.