Publications by authors named "Aliny P Lima"

3 Publications

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In vitro cytotoxicity and in vivo zebrafish toxicity evaluation of Ru(ii)/2-mercaptopyrimidine complexes.

Dalton Trans 2019 May;48(18):6026-6039

Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goias-UFG, CEP 74690-900 Goiania, Goias, Brazil.

In this paper, four new ruthenium complexes, [Ru(N-S)(dppm)2]PF6 (1), [Ru(N-S)(dppe)2]PF6 (2), [Ru(N-S)2(dppp)] (3) and [Ru(N-S)2(PPh3)2] (4) [dppm = 1,1-bis(diphenylphosphino)methane, dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, PPh3 = triphenylphosphine and N-S = 2-mercaptopyrimidine anion] were synthesized and characterized using spectroscopy techniques, molar conductance, elemental analysis, electrochemical techniques and X-ray diffraction. The DNA binding studies were investigated using voltammetry and spectroscopy techniques. The results show that all complexes exhibit a weak interaction with DNA. HSA interaction with the complexes was studied using fluorescence emission spectroscopy, where the results indicate a spontaneous interaction between the species by a static quenching mechanism. The cytotoxicity of the complexes was evaluated against A549, MDA-MB-231 and HaCat cells by MTT assay. Complexes (1) and (2), which are very active against triple negative MDA-MB-231, were subjected to further biological tests with this cell line. The cytotoxic activity triggered by the complexes was confirmed by clonogenic assay. Cell cycle analyses demonstrated marked anti-proliferative effects, especially at the G0/G1 and S phases. The morphological detection of apoptosis and necrosis - HO/PI and Annexin V-FITC/PI assay, elucidated that the type of cell death triggered by these complexes was probably by apoptosis. The in vivo toxicological assessment performed on zebrafish embryos revealed that complexes (1) and (2) did not present embryotoxic or toxic effects during embryonic and larval development showing that they are promising new prototypes of safer and more effective drugs for triple negative breast cancer treatment.
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http://dx.doi.org/10.1039/c8dt03738hDOI Listing
May 2019

Proteomic profile response of Paracoccidioides lutzii to the antifungal argentilactone.

Front Microbiol 2015 18;6:616. Epub 2015 Jun 18.

Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás Goiânia, Brazil.

The dimorphic fungi Paracoccidioides spp. are the etiological agents of paracoccidioidomycosis (PCM), a mycosis of high incidence in Brazil. The toxicity of drug treatment and the emergence of resistant organisms have led to research for new candidates for drugs. In this study, we demonstrate that the natural product argentilactone was not cytotoxic or genotoxic to MRC5 cells at the IC50 concentration to the fungus. We also verified the proteomic profile of Paracoccidioides lutzii after incubation with argentilactone using a label free quantitative proteome nanoUPLC-MS(E). The results of this study indicated that the fungus has a global metabolic adaptation in the presence of argentilactone. Enzymes of important pathways, such as glycolysis, the Krebs cycle and the glyoxylate cycle, were repressed, which drove the metabolism to the methylcytrate cycle and beta-oxidation. Proteins involved in cell rescue, defense and stress response were induced. In this study, alternative metabolic pathways adopted by the fungi were elucidated, helping to elucidate the course of action of the compound studied.
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http://dx.doi.org/10.3389/fmicb.2015.00616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471430PMC
July 2015

Cis-[RuCl(BzCN)(N-N)(P-P)]PF6 complexes: Synthesis and in vitro antitumor activity: (BzCN=benzonitrile; N-N=2,2'-bipyridine; 1,10-phenanthroline; P-P=1,4-bis(diphenylphosphino) butane, 1,2-bis(diphenylphosphino)ethane, or 1,1'-(diphenylphosphino)ferrocene).

J Inorg Biochem 2015 Aug 31;149:91-101. Epub 2015 Mar 31.

Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás - UFG, Goiânia, GO CEP 74001-970, Brazil. Electronic address:

The motivation to use ruthenium complexes in cancer treatment has led our research group to synthesize complexes with this metal and test them against several types of tumor cells, yielding promising results. In this paper the results of biological tests, assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, were carried out on the complexes cis-[RuCl(BzCN)(bipy)(dppe)]PF6 (1), cis-[RuCl(BzCN)(bipy)(dppb)]PF6 (2), cis-[RuCl(BzCN)(bipy)(dppf)]PF6 (3) and cis-[RuCl(BzCN)(phen)(dppb)]PF6 (4) which are described [BzCN = b enzonitrile; bipy = 2,2'-bipyridine; phen = 1,10-phenanthroline; dppe = 1,2-bis(diphenylphosphino) ethane; dppb = 1,4-bis-(diphenylphosphino)butane; dppf = 1,1'-bis(diphenylphosphino)ferrocene]. The present study is focused on the cytotoxic activity of complexes (1)-(4) against four tumor cell lines and on the apoptosis and changes in the cell cycle and gene expression observed in the sarcoma 180 (S180) tumor cell line treated with complex (1). The results demonstrated that this complex inhibits S180 cell growth, with an IC50 of 17.02 ± 8.21 μM, while exhibiting lower cytotoxicity (IC50 = 53.73 ± 5.71 μM) towards lymphocytes (normal cells). Flow cytometry revealed that the complex inhibits the growth of tumor cells by inducing apoptosis as evidenced by an increase in the proportion of cells positive for annexin V staining and G0/G1 phase cell-cycle arrest. Further investigation showed that complex (1) induces a drop in the mitochondrial membrane potential and provokes a decrease in Bcl-2 protein expression and increase in caspase 3 activation, while the increased activation of caspase 8 caused a decrease in the gene expression in caspases 3 and 9. Increases in Tp53 and Bax expressions were also observed.
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http://dx.doi.org/10.1016/j.jinorgbio.2015.03.011DOI Listing
August 2015