Alketa Tarushi

Interaction of Zn(II) with quinolone drugs: Structure and biological evaluation

Zinc complexes with the third-generation quinolone antibacterial drugs levofloxacin and sparfloxacin have been synthesized and characterized. The deprotonated quinolones act as bidentate ligands coordinated to zinc ion through the pyridone and a carboxylato oxygen atom. The crystal structures of [bis(aqua)bis(levofloxacinato)zinc(II)], 1, and [bis(sparfloxacinato)(1,10-phenanthroline)zinc(II)], 3, have been determined by X-ray crystallography. The biological activity of the complexes has been evaluated by examining their ability to bind to calf-thymus DNA (CT DNA) by UV spectroscopy and viscosity measurements. UV studies of the interaction of the complexes with DNA have revealed that they can bind to CT DNA probably by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. The DNA binding constants have been also calculated. A competitive study with ethidium bromide (EB) showed that the complexes exhibit the ability to displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB for the intercalative binding site. The interaction of the complexes with human and bovine serum albumin proteins has been studied by fluorescence spectroscopy showing that the complexes exhibit good binding propensity to these proteins having relatively high binding constant values. The biological properties of the complexes have been evaluated in comparison to the previously reported Zn(II) complexes with the first- and second-generation quinolones oxolinic acid and enrofloxacin.

Zinc(II) complexes with the quinolone antibacterial drug flumequine: structure, DNA- and albumin-binding

The interaction of Zn(II) with the quinolone antibacterial drug flumequine (Hflmq) in the presence or absence of an N,N′-donor heterocyclic ligand, 2,2′-bipyridine (bipy), is being investigated. Interaction of equimolar quantities of ZnCl2 with flumequine and 2,2′-bipyridine results in the formation of a structurally characterized [Zn(flmq)(bipy)Cl] (2) complex, while excess of flumequine leads to a structurally characterized [Zn(flmq)2(bipy)] (3) compound. The reaction of ZnCl2 with flumequine in the absence of 2,2′-bipyridine leads to formation of complex [Zn(flmq)2(H2O)2] (1). In all these complexes, the deprotonated bidentate flumequinato ligands are coordinated to zinc ions through pyridone and carboxylato oxygens. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. UV study of interaction of the complexes with calf-thymus DNA (CT DNA) has shown that they bind to CT DNA and [Zn(flmq)(bipy)Cl] exhibits the highest binding constant. A competitive study with ethidium bromide (EB) has shown that the complexes can displace DNA-bound EB, indicating that they bind to DNA in strong competition with EB. The complexes bind to CT DNA in an intercalative binding mode which has also been verified by DNA solution viscosity measurements. DNA electrophoretic mobility experiments showed that all complexes bind to pDNA possibly in an intercalative manner resulting in catenanes formation as well as in double-stranded cleavage reflecting (or ending) in the formation of linear DNA.

A [24-MC-6] zinc metallacoronate with a nonsteroidal antiinflammatory drug as the constructing ligand.

The interaction of ZnCl(2) with 2-dipyridylketonoxime (=Hpko) and flufenamic acid (=Hfluf) in a basic methanolic solution leads to the formation of a hexanuclear 24-membered metallacoronate, [Zn(6)(OH)(2)(pko)(4)(fluf)(6)] (1), with a [Zn-O-C-O] repeat unit and a nonsteroidal antiinflammatory drug as the constructing ligand. Compound 1 retains its structure in a dimethyl sulfoxide solution, as shown by (1)H NMR spectroscopy and molar conductance.

New copper(II) complexes of the anti-inflammatory drug mefenamic acid: a concerted study including synthesis, physicochemical characterization and their biological evaluation

Reaction of hydrated copper(II) mefenamate in the presence of diverse N-donor ligands such as N,N,N′,N′-tetramethylethylenediamine (temed), ethylenediamine (en), β-picoline (β-pic) in a methanol:water mixture (4:1, v/v) yielded crystalline monomeric copper(II) complexes [Cu(temed) (mefenamato)2], 1, [Cu(en)2(H2O)2](mefenamato)2, 2 and [Cu(β-pic)2(mefenamato)2]·H2O, 3. The newly synthesized complexes have been characterized by elemental analysis, spectroscopic methods (FT-IR, UV-Vis and EPR), thermogravimetric analyses and single-crystal X-ray structure determination in the case of complexes 2 and 3. The ground-state geometry optimization of complex 1 was performed by DFT calculations. In order to verify the complexes capability to get bound and possibly transported by the albumin towards their biological targets (cells and/or tissues), the interaction with bovine (BSA) and human serum albumin (HSA) was studied by fluorescence emission spectroscopy. The interaction of complexes 1–3 with calf-thymus DNA (CT DNA) was monitored by UV-Vis spectroscopy, cyclic voltammetry, viscosity measurements and via the ethidium bromide (EB) displacement from the EB–DNA conjugate performed by fluorescence emission spectroscopy, as a preliminary approach to evaluate their potential biological activity.

Toward Multifunctional Materials Incorporating Stepladder Manganese(III) Inverse-[9-MC-3]-Metallacrowns and Anti-Inflammatory Drugs

The interaction of Mn(ClO4)2·6H2O with salicylaldoxime (H2sao) in the presence of nonsteroidal anti-inflammatory drug (NSAID) sodium diclofenac (Nadicl) or indomethacin (Hindo) leads to the formation of the hexanuclear Mn(III) clusters [Mn6(O)2(dicl)2(sao)6(CH3OH)6] (1) and [Mn6(O)2(indo)2(sao)6(H2O)4] (2) both characterized as stepladder inverse-9-metallacrown-3 accommodating dicl- or indo- ligands, respectively. When the interaction of MnCl2·4H2O with Nadicl or Hindo is in the absence of H2sao, the mononuclear Mn(II) complexes [Mn(dicl)2(CH3OH)4] (3) and [Mn(indo)2(CH3OH)4] (4) were isolated. The complexes were characterized by physicochemical and spectroscopic techniques, and the structure of complexes 1 and 2 was characterized by X-ray crystallography. Magnetic measurements (dc and ac) were carried out in order to investigate the nature of magnetic interactions between the magnetic ions and the overall magnetic behavior of the complexes.

Structure and biological activities of metal complexes of flumequine

The reaction of CoCl2·6H2O with the quinolone antimicrobial agent flumequine (Hflmq) in the absence or presence of the α-diimines 2,2′-bipyridine (bipy), 1,10-phenanthroline (phen) or 2,2′-bipyridylamine (bipyam) resulted in the formation of four mononuclear complexes which were characterized with physicochemical and spectroscopic techniques. The crystal structures of [Co(flmq)2(bipy)]·2H2O, [Co(flmq)2(phen)]·1.6MeOH·0.4H2O and [Co(flmq)2(bipyam)]·H2O were determined by X-ray crystallography. The interaction of the complexes with calf-thymus DNA (CT DNA) was investigated by UV spectroscopy, viscosity measurements, cyclic voltammetry and competitive studies with ethidium bromide in order to evaluate the possible DNA-binding mode and to calculate the corresponding DNA-binding constants. The binding of the complexes to human or bovine serum albumin was studied by fluorescence emission spectroscopy and the corresponding binding constants were determined. The antimicrobial activity of the Co(II)–flumequine and the recently reported Cu(II)–flumequine complexes was tested against four different microorganisms (Escherichia coli, Xanthomonas campestris, Staphylococcus aureus and Bacillus subtilis) and was found to be similar to that of free Hflmq. The antiproliferative activity of previously reported complexes [Cu(flmq)(phen)Cl], [Zn(flmq)(phen)Cl] and [Ni(flmq)2(phen)] against human ovarian (A2780) and lung (A549) cancer cell lines is also reported in comparison to the cobalt analogue, [Co(flmq)(phen)Cl], 3, highlighting important differences among the various complexes which may be due to different uptake and modes of action.

A step-ladder manganese(III) metallacrown hosting mefenamic acid and a manganese(II)–mefanamato complex: synthesis, characterization and cytotoxic activity

The interaction of Mn(II) with the non-steroidal anti-inflammatory drug mefenamic acid (Hmef) in the presence or absence of salicylaldoxime (H2sao) leads to the formation of the hexanuclear Mn(III) cluster [Mn6(O)2(mef)2(sao)6(CH3OH)4] 1, characterized as stepladder inverse-9-metallacrown-3 accommodating mefenamato ligands, or the mononuclear Mn(II) complex [Mn(mef)2(CH3OH)4], 2, respectively. Both complexes were characterized by physicochemical and spectroscopic techniques and the structure of complex 1 was characterized by X-ray crystallography. The overall magnetic behavior of compound 1 is antiferromagnetic with a high-spin well-isolated ground state S = 4. The in vitro cytotoxic effects of the complexes were evaluated against three cancer cell lines (HeLa, MCF-7 and A549 cells) as well as their combinatory activity with the well-known chemotherapeutic drugs cisplatin and 5-fluorouracil. Furthermore, in silico predictive tools have been employed to study the properties and acute rat toxicity and cell line cytotoxicity of the most active complex.

In vitro and in silico study of the biological activity of manganese(III) inverse-[9-MC-3]-metallacrowns and manganese(II) complexes with the anti-inflammatory drugs diclofenac or indomethacin

In the present contribution, the biological properties of four manganese complexes with the non-steroidal anti-inflammatory drugs sodium diclofenac (Nadicl) or indomethacin (Hindo) in the presence or absence of salicylaldoxime (Η2sao), i.e. [Μn6(O)2(dicl)2(sao)6(CH3OH)6] 1, [Μn6(O)2(indo)2(sao)6(H2O)4], 2, [Μn(dicl)2(CH3OH)4], 3, and [Μn(indo)2(CH3OH)4], 4 are presented. More specifically, the in vitro cytotoxic effects of the complexes were evaluated against three cancer cell lines (HeLa, MCF-7 and A549 cells) as well as their combinatory activity with the well-known chemotherapeutic drugs irinotecan, cisplatin, paclitaxel and 5-fluorouracil. The biological activity of the complexes was investigated in vitro by studying their affinity to calf-thymus DNA and their binding towards bovine or human serum albumin (HSA). Molecular docking simulations on the crystal structure of HSA and human estrogen receptor alpha (hERa) were employed in order to study in silico the ability of the studied complexes to bind to these proteins.

Manganese coordination compounds of mefenamic acid: In vitro screening and in silico prediction of biological activity

The in vitro and in silico biological properties of two manganese complexes with the non-steroidal anti-inflammatory drug mefenamic acid (Hmef) in the presence or absence of salicylaldoxime (Η2sao), i.e. [Μn6(O)2(mef)2(sao)6(CH3OH)4] 1, and [Μn(mef)2(CH3OH)4] 2, respectively, are presented in the present contribution. More specifically, the in vitro biological activity of the complexes was investigated by studying their affinity to calf-thymus DNA (by diverse spectroscopic and physicochemical techniques) and their binding towards bovine (BSA) or human serum albumin (HSA) (by fluorescence emission spectroscopy). Molecular docking simulations on the crystal structures of HSA and DNA, exploring in silico the ability of the complexes to bind to these macromolecules, were also employed in order to explain the described in vitro activity of the compounds. Furthermore, in silico predictive tools have been employed to study the properties of the most active complex 2 to act as anticancer agent, in continuation of the previously reported cytotoxic activity. It is adopted in silico studies on a multitude of proteins involved in cancer growth, as well as prediction of drug-induced changes of gene expression profile, protein- and mRNA-based prediction results, prediction of sites of metabolism, quantitative prediction of antitarget interaction profiles etc.