Three new platinum complexes containing fluoroquinolones and DMSO: Cytotoxicity and evaluation against drug-resistant tuberculosis
| Autor: | Zumira A. Carneiro, Carla D. Lopes, Leticia P. de Oliveira, Sérgio de Albuquerque, Marcus V. N. de Souza, Drielly A. Paixão, Camila Maríngolo Ribeiro, Letícia R. Teixeira, Fernando Rogério Pavan, Maurício F. Lima, Marcos Pivatto, Wendell Guerra |
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| Přispěvatelé: | Universidade Federal de Uberlândia (UFU), Universidade de São Paulo (USP), Universidade Estadual Paulista (Unesp), Fundacao Oswaldo Cruz, Universidade Federal de Minas Gerais (UFMG) |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Ofloxacin Platinum complexes Stereochemistry Cell Survival Cytotoxicity 030106 microbiology Apoptosis Resistant strains Biochemistry Inorganic Chemistry Mycobacterium tuberculosis 03 medical and health sciences chemistry.chemical_compound Fluoroquinolone Ciprofloxacin Cell Line Tumor Tuberculosis Multidrug-Resistant medicine Potency Humans Dimethyl Sulfoxide skin and connective tissue diseases Cisplatin biology Chemistry biology.organism_classification Piperazine 030104 developmental biology Sparfloxacin Cell culture MCF-7 Cells Drug Screening Assays Antitumor medicine.drug Fluoroquinolones |
| Zdroj: | Web of Science Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| ISSN: | 1873-3344 |
| Popis: | Made available in DSpace on 2018-11-29T14:59:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-06-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) This work describes the synthesis, characterization and biological evaluation of three platinum complexes of the type [Pt(DMSO)(L)Cl]Cl, in which L represents a fluoroquinolone, namely, ciprofloxacin (cpl), ofloxacin (ofl), or sparfloxacin (spf). The new complexes were characterized by elemental analysis, high-resolution mass spectrometry (HRESIMS) and H-1, C-13 and Pt-195 NMR (nuclear magnetic resonance). The spectral data suggest that the fluoroquinolones act as bidentate ligands coordinated to Pt(II) through the nitrogen atoms of the piperazine ring. Microbiological assays against wild type Mycobacterium tuberculosis (ATCC 27294) showed that all complexes have been very potent, exhibiting antitubercular potency at concentrations < 2 mu M, although none of the complexes presented higher potency than established anti-TB drugs. As to the resistant strains, the complex with sparfloxacin, [Pt(DMSO)(spf)Cl]Cl exhibited the best potential against most Mycobacterium tuberculosis clinical isolates. The cytotoxicity of these compounds was also evaluated in three breast cell lines: MCF-10 (a healthy cell), MCF-7 (a hormone responsive cancer cell) and MDA-MB-231 (triple negative breast cancer cell). In both tumor cell lines, [Pt(DMSO)(spf)Cl]Cl was more active and more selective than cisplatin. Flow cytometry analysis revealed that [Pt(DMSO)(spf)Cl]Cl induced late apoptotic cell death in MDA-MB-231 cells. Univ Fed Uberlandia, Inst Quim, Av Joao Naves de Avila,2121,Campus Santa Monica, BR-38400902 Uberlandia, MG, Brazil Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, Ribeirao Preto, SP, Brazil Univ Estadual Paulista, Lab Pesquisa Tuberculose, Fac Ciencias Farmaceut, Campus Araraquara, Araraquara, SP, Brazil Fundacao Oswaldo Cruz, Inst Tecnol Farmacos FarManguinhos, Rio De Janeiro, RJ, Brazil Univ Fed Minas Gerais, Dept Quim, Belo Horizonte, MG, Brazil Univ Estadual Paulista, Lab Pesquisa Tuberculose, Fac Ciencias Farmaceut, Campus Araraquara, Araraquara, SP, Brazil CNPq: 442328/2014-1 FAPEMIG: APQ-00330-14 |
| Databáze: | OpenAIRE |
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