Silver(I) complexes with phthalazine and quinazoline as effective agents against pathogenic Pseudomonas aeruginosa strains
Silver(I) complexes with phthalazine and quinazoline as effective agents against pathogenic Pseudomonas aeruginosa strains
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DOI：
10.1016/j.jinorgbio.2015.11.026
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发表时间：
2016-02-01
影响因子：
3.9
通讯作者：
Nikodinovic-Runic, Jasmina
中科院分区：
文献类型：
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作者：
Glisic, Biljana D.;Senerovic, Lidija;Nikodinovic-Runic, Jasmina
合成了5个含氮杂环化合物酞嗪（phtz）和喹唑啉（qz）的银（I）配合物，并对其进行了单晶X射线衍射分析。虽然不同的AgX盐与phtz反应，但只形成通式为{[Ag（X-O）（phtz-N）]（2）（mu-phtz-N，N '）（2）}的双核银（I）配合物，X = NO_3-（1），CF_3SO_3-（2）和ClO_4-（3）。然而，qz与等摩尔量的AgCF_3SO_3和AgBF_4反应，形成多核配合物{[Ag（CF_3SO_3-O）（qz-N）]（2）}（n）（4）和{[Ag（qz-N）][BF_4]}（n）（5）。通过体外抗微生物研究评价配合物1-5对导致许多皮肤和软组织、呼吸道、伤口和医院感染的一组微生物菌株的抗微生物研究。所获得的结果表明，所有测试的银（I）配合物具有良好的抗菌活性，对所研究的菌株的MIC（最小抑制浓度）值在2.9至48.0 μ M的范围内。在所研究的菌株中，这些复合物对致病性铜绿假单胞菌（MIC = 2.9-29 μ M）特别有效，并且具有破坏对抗生素具有高固有抗性的菌株的临床相关生物膜的显著能力。另一方面，它们对真菌白色念珠菌的活性是中等的。为了确定银（I）配合物1-5的治疗潜力，还评价了它们对人肺成纤维细胞系MRC 5的抗增殖作用。通过凝胶电泳技术证明复合物1-5与铜绿假单胞菌基因组DNA的结合，并通过分子对接到DNA小沟中得到很好的支持。所有研究的复合物显示出改善的细胞毒性相比，临床使用的硝酸银。(C)2015 Elsevier Inc. All rights reserved.
Five silver(I) complexes with aromatic nitrogen-containing heterocycles, phthalazine (phtz) and quinazoline (qz), were synthesized, characterized and analyzed by single-crystal X-ray diffraction analysis. Although different AgX salts reacted with phtz, only dinuclear silver(I) complexes of the general formula {[Ag(X-O)(phtz-N)](2)(mu-phtz-N,N')(2)} were formed, X = NO3- (1), CF3SO3- (2) and ClO4- (3). However, reactions of qz with an equimolar amount of AgCF3SO3 and AgBF4 resulted in the formation of polynuclear complexes, {[Ag(CF3SO3-O)(qz-N)](2)}(n) (4) and {[Ag(qz-N)][BF4]}(n) (5). Complexes 1-5 were evaluated by in vitro antimicrobial studies against a panel of microbial strains that lead to many skin and soft tissue, respiratory, wound and nosocomial infections. The obtained results indicate that all tested silver(I) complexes have good antibacterial activity with MIC (minimum inhibitory concentration) values in the range from 2.9 to 48.0 mu M against the investigated strains. Among the investigated strains, these complexes were particularly efficient against pathogenic Pseudomonas aeruginosa (MIC = 2.9-29 mu M) and had a marked ability to disrupt clinically relevant biofilms of strains with high inherent resistance to antibiotics. On the other hand, their activity against the fungus Candida albicans was moderate. In order to determine the therapeutic potential of silver(I) complexes 1-5, their antiproliferative effect on the human lung fibroblastic cell line MRC5, has been also evaluated. The binding of complexes 1-5 to the genomic DNA of P. aeruginosa was demonstrated by gel electrophoresis techniques and well supported by molecular docking into the DNA minor groove. All investigated complexes showed an improved cytotoxicity profile in comparison to the clinically used AgNO3. (C) 2015 Elsevier Inc. All rights reserved.