Amtul Zareen, Follmer Cristian, Mahboob Sumera, Mazhar Muhammad, Khan Khalid M, Siddiqui Rafat A, Muhammad Sajjad, Kazmi Syed A, Choudhary Mohammad Iqbal
International Center for Chemical Sciences, HEJ Research Institute of Chemistry, University of Karachi, Karachi 75270, Pakistan.
Biochem Biophys Res Commun. 2007 May 4;356(2):457-63. doi: 10.1016/j.bbrc.2007.02.158. Epub 2007 Mar 8.
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.
有机锗化合物已被用作药物制剂。然而，关于含有机锗内酯的合成及抗菌活性的报道非常少。本研究的目的是确定不同内酯取代的有机锗对细菌生长及其脲酶活性的影响。我们报告了12种锗-γ-内酯（GeL）的合成及其对几种细菌病原体的抗菌活性。所有GeL的抗菌作用对革兰氏阴性杆菌具有高度选择性，特别是奇异变形杆菌，这是一种感染泌尿道的重要病原体。此外，我们的数据表明，8-喹啉衍生物对奇异变形杆菌的活性比2-甲基-8-喹啉更强。例如，β-（邻甲基苯基）-γ，γ-双（8-喹啉氧基）锗-γ-内酯和β-（邻甲氧基苯基）-γ，γ-双（8-喹啉氧基）锗-γ-内酯的最大活性分别为MIC（90）61和94 microM。体外研究表明抗菌活性与奇异变形杆菌脲酶的抑制之间存在线性关系。进一步的动力学分析表明，抑制作用以非竞争性和浓度依赖性方式发生，β-（邻甲氧基苯基）-γ，γ-双（8-喹啉氧基）锗-γ-内酯的最小IC（50）为31 microM。总之，这些发现表明GeL有潜力被开发为抗奇异变形杆菌感染的抗菌剂。
