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Vinteler E.,Babes - Bolyai University | Stan N.-F.,Babes - Bolyai University | Luchian R.,Babes - Bolyai University | Cainap C.,The Oncology Institute Prof Dr Ion Chiricuta | And 2 more authors.
Journal of Molecular Modeling | Year: 2015

The conformational changes of imatinib (IMT) are crucial for understanding the ligand–receptor interaction and its mechanism of action [Agofonov et al. (2014) Nature Struct Mol Biol 21:848–853]. Therefore, here we investigated the free energy conformational landscape of the free IMT base, aiming to describe the three-dimensional structures and energetic stability of its conformers. Forty-five unique conformers, within an energy window of 4.8 kcal mol−1 were identified by a conformational search in gas-phase, at the B3LYP/6-31G(d) theoretical level. Among these, the 20 most stable, as well as 4 conformers resulting from optimization of experimental structures found in the two known polymorphs of IMT and in the c-Abl complex were further refined using the 6-31+G(d,p) basis set and the polarizable continuum solvation model. The most stable conformers in gas-phase and water exhibit a V-shaped structure. The major difference between the most stable free conformers and the bioactive conformers consists in the relative orientation of the pyrimidine–pyridine groups responsible for hydrogen bonding interactions in the ATP-binding pocket. The ratio of mole fractions corresponding to the two known (α and β) polymorphic forms of IMT was estimated from the calculated thermochemical data, in quantitative agreement with the existing experimental data related to their solubility. The electronic absorption spectrum of this compound was investigated in water and explained based on the theoretical TD-DFT results, considering the Boltzmann population-averaged computed data at CAM-B3LYP/6-31+G(d,p) level of theory for the nine most stable conformers. © 2015, Springer-Verlag Berlin Heidelberg.

Stanila A.,University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca | Braicu C.,The Oncology Institute Prof Dr Ion Chiricuta | Stanila S.,University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca | Pop R.M.,University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca
Notulae Botanicae Horti Agrobotanici Cluj-Napoca | Year: 2011

The antibacterial properties of differently copper and cobalt amino acids complexes on agar plates was investigated in the present study. The antibacterial activity of amino acid complexes was evaluated against on three bacteria strains (Escherichia coli, Bacillus cereus, Micrococcus luteus). Generally, the amino acids complexes were mainly active against gram-positive organisms, species like Micrococcus luteus being the most susceptible strain tested. It was registered a moderate antibacterial activity against Bacillus cereus. The microorganisms Escherichia coli, which are already known to be multi-resistant to drugs, were also resistant to the amino acids complexes but also to the free salts tested. Escherichia coli were susceptible only to the CoCl2 and copper complex with phenylalanine. The complexes with leucine and histidine seem to be more active than the parent free ligand against one or more bacterial species. Moderate activity was registered in the case of complexes with methionine and phenylalanine. From the complexes tested less efficient antibacterial activity was noted in the case of complexes with lysine and valine. These results show that cobalt and copper complexes have an antibacterial activity and suggest their potential application as antibacterial agents.

Braicu C.,University of Medicine and Pharmacy, Cluj-Napoca | Catana C.,University of Medicine and Pharmacy, Cluj-Napoca | Calin G.A.,University of Houston | Berindan-Neagoe I.,University of Medicine and Pharmacy, Cluj-Napoca | Berindan-Neagoe I.,The Oncology Institute Prof Dr Ion Chiricuta
Current Pharmaceutical Design | Year: 2014

Cancer initiation and progression are governed by a complex multistep process in which successive alterations accumulate in multiple protein-coding and noncoding genes. MicroRNAs are an evolutionarily conserved class of endogenous 19- to 24-nucleotide noncoding RNAs that have been validated as key players in the balance of most cellular processes, including drug resistance. MicroRNAs change the output of protein-coding genes through posttranscriptional regulation by binding in a sequence-specific manner to the transcripts of their target genes. Resistance to therapy remains a major challenge in cancer treatment; clear solutions to this problem have yet to be found, in spite of intensive research in recent years. In this review, we explore the concept of cancer multitherapy using noncoding RNAs. We also address basic scientific questions that are related to personalized cancer treatment. © 2014 Bentham Science Publishers.

Lupse M.,University of Medicine and Pharmacy, Cluj-Napoca | Briciu V.,University of Medicine and Pharmacy, Cluj-Napoca | Flonta M.,University Hospital of Infectious Diseases | Nastase V.,University Hospital of Infectious Diseases | And 2 more authors.
Revista Romana de Medicina de Laborator | Year: 2014

Erythema migrans (EM) is the most common and recognized clinical manifestation of early Lyme Borreliosis (LB) in Europe. Purpose: to evaluate clinically and serologically all the patients with EM and to correlate the serology with clinical approach. Material and method: A prospective analyses of all patients that came with EM in our University Hospital of Infectious Diseases from Cluj-Napoca Romania between 1st of April to 31st of August 2011. We registered data regarding: age, gender, interval between tick bite and EM occurrence, interval between EM appearance and hospital presentation, serology (IgM and IgG for Borrelia burgdorferi sl) at presentation and one year after, antibiotic treatment, duration of antibiotic treatment and clinical outcome. Results: 44 patients with EM, 2 had Multiple EM, 23 male (52 %), average age 41.3 years (min 3 years, max 84 years, median 43.5 years). Serology at presentation was positive in 15 patients for IgM and in 9 patients for IgG with ELISA and for 13 for IgM and 16 for IgG with WB. At the one year follow up positive results for IgM were found in 14 patients with ELISA and in 11 patients with WB. IgG was positive in 7 patients with ELISA and in 5 with WB. The average time interval between the tick bite and EM was not significant different for patients with negative or positive IgM or IgG. The interval between EM occurrence and treatment initiation had a strong significance for IgG. After one year no statistical significance was found for positive IgM for any of the analyzed factors while for IgG positivity we found a significant importance for age and duration of incubation. No influence of antibiotic or duration of treatment was found on serology of our patients. Conclusions: Our data brings additional evidence that the serological profile is unpredictable.

Belean B.,Romanian Institute of Isotopic And Molecular Technology | Borda M.,Technical University of Cluj Napoca | Ackermann J.,Goethe University Frankfurt | Koch I.,Goethe University Frankfurt | Balacescu O.,The Oncology Institute Prof Dr Ion Chiricuta
BMC Bioinformatics | Year: 2015

Background: Microarray analysis represents a powerful way to test scientific hypotheses on the functionality of cells. The measurements consider the whole genome, and the large number of generated data requires sophisticated analysis. To date, no gold-standard for the analysis of microarray images has been established. Due to the lack of a standard approach there is a strong need to identify new processing algorithms. Methods: We propose a novel approach based on hyperbolic partial differential equations (PDEs) for unsupervised spot segmentation. Prior to segmentation, morphological operations were applied for the identification of co-localized groups of spots. A grid alignment was performed to determine the borderlines between rows and columns of spots. PDEs were applied to detect the inflection points within each column and row; vertical and horizontal luminance profiles were evolved respectively. The inflection points of the profiles determined borderlines that confined a spot within adapted rectangular areas. A subsequent k-means clustering determined the pixels of each individual spot and its local background. Results: We evaluated the approach for a data set of microarray images taken from the Stanford Microarray Database (SMD). The data set is based on two studies on global gene expression profiles of Arabidopsis Thaliana. We computed values for spot intensity, regression ratio, and coefficient of determination. For spots with irregular contours and inner holes, we found intensity values that were significantly different from those determined by the GenePix Pro microarray analysis software. We determined the set of differentially expressed genes from our intensities and identified more activated genes than were predicted by the GenePix software. Conclusions: Our method represents a worthwhile alternative and complement to standard approaches used in industry and academy. We highlight the importance of our spot segmentation approach, which identified supplementary important genes, to better explains the molecular mechanisms that are activated in a defense responses to virus and pathogen infection. © 2015 Belean et al.

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