Publications by authors named "Valentina Uivarosi"

12 Publications

  • Page 1 of 1

Improvement in the Pharmacological Profile of Copper Biological Active Complexes by Their Incorporation into Organic or Inorganic Matrix.

Molecules 2020 Dec 10;25(24). Epub 2020 Dec 10.

Department of Inorganic Chemistry, Faculty of Chemistry, University of Bucharest, 90-92 Panduri Str., 050663 Bucharest, Romania.

Every year, more Cu(II) complexes are proven to be biologically active species, but very few are developed as drugs or entered in clinical trials. This is due to their poor water solubility and lipophilicity, low stability as well as in vivo inactivation. The possibility to improve their pharmacological and/or oral administration profile by incorporation into inorganic or organic matrix was studied. Most of them are either physically encapsulated or conjugated to the matrix via a moiety able to coordinate Cu(II). As a result, a large variety of species were developed as delivery carriers. The organic carriers include liposomes, synthetic or natural polymers or dendrimers, while the inorganic ones are based on carbon nanotubes, hydrotalcite and silica. Some hybrid organic-inorganic materials based on alginate-carbonate, gold-PEG and magnetic mesoporous silica-Schiff base were also developed for this purpose.
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http://dx.doi.org/10.3390/molecules25245830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763451PMC
December 2020

Rare-Earth Metal Complexes of the Antibacterial Drug Oxolinic Acid: Synthesis, Characterization, DNA/Protein Binding and Cytotoxicity Studies.

Molecules 2020 Nov 19;25(22). Epub 2020 Nov 19.

Department of General and Inorganic Chemistry, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia St, 020956 Bucharest, Romania.

"Drug repositioning" is a current trend which proved useful in the search for new applications for existing, failed, no longer in use or abandoned drugs, particularly when addressing issues such as bacterial or cancer cells resistance to current therapeutic approaches. In this context, six new complexes of the first-generation quinolone oxolinic acid with rare-earth metal cations (Y, La, Sm, Eu, Gd, Tb) have been synthesized and characterized. The experimental data suggest that the quinolone acts as a bidentate ligand, binding to the metal ion via the keto and carboxylate oxygen atoms; these findings are supported by DFT (density functional theory) calculations for the Sm complex. The cytotoxic activity of the complexes, as well as the ligand, has been studied on MDA-MB 231 (human breast adenocarcinoma), LoVo (human colon adenocarcinoma) and HUVEC (normal human umbilical vein endothelial cells) cell lines. UV-Vis spectroscopy and competitive binding studies show that the complexes display binding affinities (K) towards double stranded DNA in the range of 9.33 × 10 - 10.72 × 10. Major and minor groove-binding most likely play a significant role in the interactions of the complexes with DNA. Moreover, the complexes bind human serum albumin more avidly than apo-transferrin.
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http://dx.doi.org/10.3390/molecules25225418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699381PMC
November 2020

Synthesis, Characterization, Cytotoxic Activity, and Metabolic Studies of Ruthenium(II) Polypyridyl Complexes Containing Flavonoid Ligands.

Inorg Chem 2020 Apr 19;59(7):4424-4434. Epub 2020 Mar 19.

Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology, F-75005 Paris, France.

Four novel monocationic Ru(II) polypyridyl complexes were synthesized with the general formula [Ru(DIP)flv]X, where DIP is 4,7-diphenyl-1,10-phenanthroline, flv stands for the flavonoid ligand (5-hydroxyflavone in [Ru(DIP)(5-OHF)](PF), genistein in [Ru(DIP)(gen)](PF), chrysin in [Ru(DIP)(chr)](OTf), and morin in [Ru(DIP)(mor)](OTf)), and X is the counterion, PF, and OTf ̅ (triflate, CFSO̅), respectively. Following the chemical characterization of the complexes by H and C NMR, mass spectrometry, and elemental analysis, their cytotoxicity was tested against several cancer cell lines. The most promising complex, [Ru(DIP)(gen)](PF), was further investigated for its biological activity. Metabolic studies revealed that this complex severely impaired mitochondrial respiration and glycolysis processes, contrary to its precursor, Ru(DIP)Cl, which showed a prominent effect only on the mitochondrial respiration. In addition, its preferential accumulation in MDA-MB-435S cells (a human melanoma cell line previously described as mammary gland/breast; derived from metastatic site: pleural effusion), which are used for the study of metastasis, explained the better activity in this cell line compared to MCF-7 (human, ductal carcinoma).
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http://dx.doi.org/10.1021/acs.inorgchem.9b03562DOI Listing
April 2020

Quinolone Complexes with Lanthanide Ions: An Insight into their Analytical Applications and Biological Activity.

Molecules 2020 Mar 16;25(6). Epub 2020 Mar 16.

Department of General and Inorganic Chemistry, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia St, Bucharest 020956, Romania.

Quinolones comprise a series of synthetic bactericidal agents with a broad spectrum of activity and good bioavailability. An important feature of these molecules is their capacity to bind metal ions in complexes with relevant biological and analytical applications. Interestingly, lanthanide ions possess extremely attractive properties that result from the behavior of the internal 4f electrons, behavior which is not lost upon ionization, nor after coordination. Subsequently, a more detailed discussion about metal complexes of quinolones with lanthanide ions in terms of chemical and biological properties is made. These complexes present a series of characteristics, such as narrow and highly structured emission bands; large gaps between absorption and emission wavelengths (Stokes shifts); and long excited-state lifetimes, which render them suitable for highly sensitive and selective analytical methods of quantitation. Moreover, quinolones have been widely prescribed in both human and animal treatments, which has led to an increase in their impact on the environment, and therefore to a growing interest in the development of new methods for their quantitative determination. Therefore, analytical applications for the quantitative determination of quinolones, lanthanide and miscellaneous ions and nucleic acids, along with other applications, are reviewed here.
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http://dx.doi.org/10.3390/molecules25061347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144119PMC
March 2020

Synthesis and Structural Investigation of New Bio-Relevant Complexes of Lanthanides with 5-Hydroxyflavone: DNA Binding and Protein Interaction Studies.

Molecules 2016 Dec 16;21(12). Epub 2016 Dec 16.

Department of General and Inorganic Chemistry, Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, 6 Traian Vuia Str., 020956 Bucharest, Romania.

In the present work, we attempted to develop new metal coordination complexes of the natural flavonoid 5-hydroxyflavone with Sm(III), Eu(III), Gd(III), Tb(III). The resultant hydroxo complexes have been characterized by a variety of spectroscopic techniques, including fluorescence, FT-IR, UV-Vis, EPR and mass spectral studies. The general chemical formula of the complexes is [Ln(CH₉O₃)₃(OH)₂(H₂O)]·H₂O, where Ln is the lanthanide cation and x = 0 for Sm(III), x = 1 for Eu(III), Gd(III), Tb(III) and = 0 for Sm(III), Gd(III), Tb(III), = 1 for Eu(III), respectively. The proposed structures of the complexes were optimized by DFT calculations. Theoretical calculations and experimental determinations sustain the proposed structures of the hydroxo complexes, with two molecules of 5-hydroxyflavone acting as monoanionic bidentate chelate ligands. The interaction of the complexes with calf thymus DNA has been explored by fluorescence titration and UV-Vis absorption binding studies, and revealed that the synthesized complexes interact with DNA with binding constants (K) ~ 10⁴. Human serum albumin (HSA) and transferrin (Tf) binding studies have also been performed by fluorescence titration techniques (fluorescence quenching studies, synchronous fluorescence spectra). The apparent association constants (K) and thermodynamic parameters have been calculated from the fluorescence quenching experiment at 299 K, 308 K, and 318 K. The quenching curves indicate that the complexes bind to HSA with smaller affinity than the ligand, but to Tf with higher binding affinities than the ligand.
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http://dx.doi.org/10.3390/molecules21121737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273368PMC
December 2016

Recent progress in understanding the molecular mechanisms of radioresistance in Deinococcus bacteria.

Extremophiles 2015 Jul 4;19(4):707-19. Epub 2015 Jun 4.

Department of Industrial Drugs and Pharmaceutical Biotechnology, Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, 6, Traian Vuia Str., 020956, Bucharest, Romania,

The deleterious effects of ionizing radiation are a major concern of the modern world. In the last decades, outstanding interest has been given to developing new therapeutic tools designed for protection against the toxic effects of ionizing radiation. Deinococcus spp. are among the most radioresistant organisms on Earth, being able to survive extreme doses of radiation, 1000-fold higher than most vertebrates. The molecular mechanisms underlying DNA repair and biomolecular protection, which are responsible for the remarkable radioresistance of Deinococcus bacteria, have been a debatable subject for the last 60 years. This paper is focused on the most recent findings regarding the molecular background of radioresistance and on Deinococcus bacteria response to oxidative stress. Novel proteins and genes involved in the highly regulated DNA repair processes, and enzymatic and non- enzymatic antioxidant systems are presented. In addition, a recently proposed mechanism that may contribute to oxidative damage protection in Deinococcus bacteria is discussed. A better understanding of these molecular mechanisms may draw future perspectives for counteracting radiation-related toxicity.
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http://dx.doi.org/10.1007/s00792-015-0759-9DOI Listing
July 2015

Biochemical action of new complexes of ruthenium with quinolones as potential antitumor agents.

Anticancer Res 2015 Jun;35(6):3371-8

Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

Background: The aim of the present study paper was to identify the role of reactive oxygen species (ROS) in apoptosis signaling mechanisms. We used for this purpose two ruthenium complex compounds based on that overproduce these reactive species by their metabolism thus manifesting their antitumor activity too.

Materials And Methods: In vivo studies were performed in Walker 256 carcinoma-bearing Wistar rats treated with two ruthenium (III) (Ru(III)) complexes with -fluoroquinolones norfloxacin and ofloxacin. The treatment started 7 days after tumor grafting. We assayed the dynamics of apoptosis by flow-cytometry and the biochemical oxidative status parameters. The biological samples used were serum and whole-tumor tissues; the results were compared to the untreated control group.

Results: The results showed an increase of apoptosis from 14.79% to 59.72% 14.79% to 59.72% in tumor cells treated with the most active combination, ruthenium complex with norfloxacin. We also noted an increase of the oxidative status and ROS production during treatment.

Conclusion: The newly-synthesized complexes are less toxic and their activity is based on the induction of oxidative stress.
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June 2015

Pharmacokinetic profile evaluation of di-μ-hydroxo-bis(quercetinatooxovanadium(IV)) complex.

Curr Health Sci J 2014 Oct-Dec;40(4):265-70. Epub 2014 Dec 14.

"Carol Davila" University of Medicine and Pharmacy, Faculty of Pharmacy.

The present study was designed to evaluate the pharmacokinetic (PK) properties of di-μ-hydroxo-bis(quercetinatooxovanadium(IV) (HOBQOV) complex, with hypoglycemic and hypolipidemic properties, in rats after a single i.p. dose of 100 mg/kg b.w. The HOBQOV complex pharmacokinetics is described by a bicompartmental model and the plasma concentration decrease is described by two phases that might be correlated to the distribution and elimination processes. The obtained results suggest a PK profile of the complex suitable for a profound distribution in the animal organism with possibility of interaction with the cytosolic enzymes.
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http://dx.doi.org/10.12865/CHSJ.40.04.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709704PMC
January 2016

Synthesis and antioxidant activity evaluation of new compounds from hydrazinecarbothioamide and 1,2,4-triazole class containing diarylsulfone and 2,4-difluorophenyl moieties.

Int J Mol Sci 2014 Jun 17;15(6):10908-25. Epub 2014 Jun 17.

Organic Chemistry Department, Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, 6 Traian Vuia, 020956 Bucharest, Romania.

In the present investigation, new hydrazinecarbothioamides 4-6 were synthesized by reaction of 4-(4-X-phenylsulfonyl)benzoic acids hydrazides (X=H, Cl, Br) 1-3 with 2,4-difluorophenyl isothiocyanate and further these were treated with sodium hydroxide to obtain 1,2,4-triazole-3-thione derivatives 7-9. The reaction of 7-9 with α-halogenated ketones, in basic media, afforded new S-alkylated derivatives 10-15. The structures of the synthesized compounds have been established on the basis of 1H-NMR, 13C-NMR, IR, mass spectral studies and elemental analysis. The antioxidant activity of all compounds has been screened. Hydrazinecarbothioamides 4-6 showed excellent antioxidant activity and 1,2,4-triazole-3-thiones 7-9 showed good antioxidant activity using the DPPH method.
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http://dx.doi.org/10.3390/ijms150610908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100188PMC
June 2014

Metal complexes of quinolone antibiotics and their applications: an update.

Molecules 2013 Sep 11;18(9):11153-97. Epub 2013 Sep 11.

Department of General and Inorganic Chemistry, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia St, Bucharest 020956, Romania.

Quinolones are synthetic broad-spectrum antibiotics with good oral absorption and excellent bioavailability. Due to the chemical functions found on their nucleus (a carboxylic acid function at the 3-position, and in most cases a basic piperazinyl ring (or another N-heterocycle) at the 7-position, and a carbonyl oxygen atom at the 4-position) quinolones bind metal ions forming complexes in which they can act as bidentate, as unidentate and as bridging ligand, respectively. In the polymeric complexes in solid state, multiple modes of coordination are simultaneously possible. In strongly acidic conditions, quinolone molecules possessing a basic side nucleus are protonated and appear as cations in the ionic complexes. Interaction with metal ions has some important consequences for the solubility, pharmacokinetics and bioavailability of quinolones, and is also involved in the mechanism of action of these bactericidal agents. Many metal complexes with equal or enhanced antimicrobial activity compared to the parent quinolones were obtained. New strategies in the design of metal complexes of quinolones have led to compounds with anticancer activity. Analytical applications of complexation with metal ions were oriented toward two main directions: determination of quinolones based on complexation with metal ions or, reversely, determination of metal ions based on complexation with quinolones.
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http://dx.doi.org/10.3390/molecules180911153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269848PMC
September 2013

Synthesis and characterization of some new complexes of magnesium (II) and zinc (II) with the natural flavonoid primuletin.

Molecules 2013 Jul 1;18(7):7631-45. Epub 2013 Jul 1.

Department of General and Inorganic Chemistry, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia St, Bucharest 020956, Romania.

Two new metal complexes formulated as [Mg(L)2(H2O)2]·H2O (1) and [Zn(L)2(H2O)2]·0.5H2O (2), where HL = 5-hydroxyflavone (primuletin), have been synthesized and characterized by elemental and thermal analyses, molar conductance, IR, UV-Vis, 1H- and 13C-NMR, fluorescence and mass spectra. In solid state, complexes had shown higher fluorescence intensities comparing to the free ligand, and this behavior is appreciated as a consequence of the coordination process.
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http://dx.doi.org/10.3390/molecules18077631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270113PMC
July 2013

Synthesis, spectral and thermal studies of new rutin vanadyl complexes.

Molecules 2010 Mar 10;15(3):1578-89. Epub 2010 Mar 10.

Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia St, 020956 Bucharest, Romania.

Complexes between oxovanadium (IV) cation and flavonoid derivatives were developed recently in order to increase the intestinal absorption and to reduce the toxicity of vanadium compounds. For these reasons, is interesting to investigate the complexation process between flavonoid rutin (Rut) and vanadyl cation in order to isolate new complexes. Two new complexes [VO(Rut)(H2O)2](SO4)0.5 x 2 H2O and [VO(Rut)2] x 4 H2O have been obtained and characterized by elemental and thermal analyses and several spectroscopic techniques (ESI-MS, IR, UV-Vis, fluorescence). The studies concerning complex formation between vanadyl and rutin (Rut) performed in different solutions show the formation of mononuclear complexes with 1:1 and 1:2 metal to ligand stoichiometry.
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http://dx.doi.org/10.3390/molecules15031578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257295PMC
March 2010