First Ruthenium Organometallic Complex of Antibacterial Agent Ofloxacin. Crystal Structure and Interactions with DNA

Abstract

Organometallic ruthenium complex of quinolone antibacterial agent ofloxacin [(η6-p-cymene)RuCl(O,O-oflo)]·2.8H2O (1·2.8H2O) was isolated and its crystal structure was determined. In this »piano-stool« complex, quinolone is bidentately coordinated to the metal through the ring carbonyl and one of the carboxylic oxygen atoms. Interactions of the title complex with DNA were studied by spectroscopic methods (electronic, fluorescence, CD) and atomic force microscopy (AFM). It was established that the electrostatic attraction between the ruthenium complex and DNA in a solution is important for the binding since interactions were observed only in a solution with low ionic strengths. An induced CD (ICD) signal was observed in the solution of DNA and title complex which proves the interaction between ruthenium and macromolecule. Competitive binding between cisplatin and 1 to DNA revealed that cisplatin prevents binding of 1. Our experiments revealed that binding of the title complex to DNA occurs also if guanine N7 is protonated. AFM has shown that title complex provokes DNA shrinkage. Preliminary biological tests have also been performed.

Synthesis, characterization and DNA-binding properties of Ru(II) complexes coordinated by ofloxacin as potential antitumor agents

“…Complexes 1-3 exhibited higher inhibitory effects than ofloxacin at the same concentrations of 50 and 100 μM. Moreover, 3 exhibited the best inhibition, which indicated that increasing of the aromatic ring can enhance the antitumor activity of Ru(II) complexes [27][28][29].…”

Antimicrobial Organometallic Dendrimers with Tunable Activity against Multidrug-Resistant Bacteria

“…3 In contrast, some organometallic compounds are evaluated as chemotherapeutics for a number of diseases, such as cancer 8 and malaria, 9 and are therefore, considered as potential antimicrobial agents. [10][11][12][13][14] Synthetic organometallic antimicrobial agents are structurally unique, leading to new mechanism of action that bypass resistance mechanism, ultimately resulting in potent activity against multidrug-resistant microbes. Regrettably, research on this class of antimicrobial is still at the early stage, 15 focusing 4 on small molecules or conventional macromolecular scaffolds, 11 and consequently, the unexplored potential of this class still needs to be evaluated.…”

Structure, antimicrobial activity, DNA- and albumin-binding of manganese(II) complexes with the quinolone antimicrobial agents oxolinic acid and enrofloxacin

“…Since the main targets of quinolones are the enzymes gyrase (type II topoisomerases) and topoisomerase IV participating in the DNA replication [4], the interaction with DNA and the antibacterial activity tested on diverse microorganisms are of great importance and thoroughly studied [5]. Based on the increased activity shown by metal complexes of drugs in comparison to their parent compounds [6], diverse metal complexes with quinolones as ligands have been synthesized and characterized and the interaction with DNA [7][8][9][10] and serum albumin proteins [11][12][13][14], the antibacterial activity [15][16][17], and the potential antitumor activity [18][19][20] have been evaluated in comparison to free quinolones.…”