title: Germa-gamma-lactones as novel inhibitors of bacterial urease activity.
abstract: 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-gamma-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 beta-(o-methylphenyl)-gamma,gamma-bis(8-quinolinoxy)germa-gamma-lactone and beta-(o-methoxyphenyl)-gamma,gamma-bis(8-quinolinoxy)germa-gamma-lactone were maximally active with MIC(90) of 61 and 94 microM, 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 IC(50) of 31 microM for beta-(o-methoxyphenyl)-gamma,gamma-bis(8-quinolinoxy)germa-gamma-lactone. In conclusion, these findings suggest that GeL have potential to be developed as antimicrobial agents against P. mirabilis infection.
authors: International Center for Chemical Sciences, HEJ Research Institute of Chemistry, University of Karachi, Karachi 75270, Pakistan. zareen_amtul@fulbrightweb.org
authors: Zareen
authors: Z
authors: Amtul
authors: Cristian
authors: C
authors: Follmer
authors: Sumera
authors: S
authors: Mahboob
authors: Atta-Ur-Rahman
authors: Muhammad
authors: M
authors: Mazhar
authors: Khalid M
authors: KM
authors: Khan
authors: Rafat A
authors: RA
authors: Siddiqui
authors: Sajjad
authors: S
authors: Muhammad
authors: Syed A
authors: SA
authors: Kazmi
authors: Mohammad Iqbal
authors: MI
authors: Choudhary
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D011513:Proteus mirabilis / Q000187:drug effects / Q000502:physiology; D014510:Urease / Q000037:antagonists & inhibitors*
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D007783:Lactones; D014510:Urease