Feio Maria J, Sousa Isabel, Ferreira Mariana, Cunha-Silva Luís, Saraiva Raúl G, Queirós Carla, Alexandre José G, Claro Vasco, Mendes Adélia, Ortiz Rosa, Lopes Sandra, Amaral Ana Luísa, Lino João, Fernandes Patrícia, Silva Ana João, Moutinho Lisete, de Castro Baltazar, Pereira Eulália, Perelló Lourdes, Gameiro Paula
REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal.
Departamento de Química Inorgánica, Facultad de Farmácia, Universidad de Valencia, Avda. Vicent Andrés Estellés S/N, 46100 Burjassot, Valencia, Spain.
J Inorg Biochem. 2014 Sep;138:129-143. doi: 10.1016/j.jinorgbio.2014.05.007. Epub 2014 May 27.
Microbial resistance to antibiotics is one of the biggest public health threats of the modern world. Antibiotic resistance is an area of much clinical relevance and therefore research that has the potential to identify agents that may circumvent it or treat resistant infections is paramount. Solution behavior of various fluoroquinolone (FQ) complexes with copper(II) in the presence and absence of 1,10-phenanthroline (phen) was studied in aqueous solution, by potentiometry and/or spectrophotometry, and are herein described. The results obtained showed that under physiological conditions (micromolar concentration range and pH7.4) only copper(II):FQ:phen ternary complexes are stable. Hence, these complexes were synthesised and characterised by means of UV-visible and IR spectroscopy, elemental analysis and single-crystal X-ray diffraction. In these complexes, the FQ acts as a bidentate ligand that coordinates the metal cation through the carbonyl and carboxyl oxygen atoms and phen coordinates through two N-atoms forming the equatorial plane of a distorted square-pyramidal geometry. The fifth position of the penta-coordinated Cu(II) centre is generally occupied axially by an oxygen atom from a water molecule or from a nitrate ion. Minimum inhibitory concentration (MIC) determinations of the complexes and comparison with free FQ in various E. coli strains indicate that the Cu-complexes are as efficient antimicrobials as the free antibiotic. Moreover, results strongly suggest that the cell intake route of both species is different supporting, therefore, the complexes' suitability as candidates for further biological testing in FQ-resistant microorganisms.
微生物对抗生素的耐药性是现代世界最大的公共卫生威胁之一。抗生素耐药性是一个具有重要临床意义的领域，因此，开展有潜力识别可规避耐药性或治疗耐药感染药物的研究至关重要。本文通过电位滴定法和/或分光光度法，研究了在有和没有1,10 - 菲啰啉（邻菲啰啉）存在的情况下，各种氟喹诺酮（FQ）与铜（II）配合物在水溶液中的溶液行为。所获得的结果表明，在生理条件下（微摩尔浓度范围和pH7.4），只有铜（II）：FQ：邻菲啰啉三元配合物是稳定的。因此，合成了这些配合物，并通过紫外可见光谱、红外光谱、元素分析和单晶X射线衍射对其进行了表征。在这些配合物中，FQ作为双齿配体，通过羰基和羧基氧原子与金属阳离子配位，邻菲啰啉通过两个N原子配位，形成扭曲的四方锥几何构型的赤道平面。五配位铜（II）中心的第五个位置通常由来自水分子或硝酸根离子的氧原子轴向占据。对这些配合物的最低抑菌浓度（MIC）进行测定，并与各种大肠杆菌菌株中的游离FQ进行比较，结果表明铜配合物与游离抗生素一样是有效的抗菌剂。此外，结果强烈表明，这两种物质的细胞摄取途径不同，因此支持这些配合物作为耐FQ微生物进一步生物学测试候选物的适用性。
