RESUMO
BACKGROUND: Thiazolidine-2,4-dione ring system is used as a pharmacophore to build various heterocyclic compounds aimed to interact with biological targets. In the present study, benzylidene-2,4-thiazolidinedione derivatives (compounds 2-5) were synthesized and screened against cancer cell lines and the genotoxicity and cytotoxicity of the most active compound (5) was investigated on normal and lung cancer cell line. METHODS: For in vitro cytotoxic screening, the MTT assay was used for HL60 and K562 (leukemia), MCF-7 (breast adenocarcinoma), HT29 (colon adenocarcinoma), HEp-2 (cervix carcinoma) and NCI-H292 (lung carcinoma) tumor cell lines and Alamar-blue assay was used for non-tumor cells (PBMC, human peripheral blood mononuclear cells) were used. Cell morphology was visualized after Giemsa-May-Grunwald staining. DNA content, phosphatidylserine externalization and mitochondrial depolarization were measured by flow cytometry. Genotoxicity was assessed by Comet assay. RESULTS: 5-(2-Bromo-5-methoxybenzylidene)-thiazolidine-2,4-dione (5) presented the most potent cytotoxicity, especially against NCI-H292 lung cancer cell line, with IC50 value of 1.26µg/mL after 72h incubation. None of the compounds were cytotoxic to PBMC. After 48h incubation, externalization of phosphatidylserine, mitochondrial depolarization, internucleosomal DNA fragmentation and morphological alterations consistent with apoptosis were observed in NCI-H292 cells treated with compound (5). In addition, compound (5) also induced genotoxicity in NCI-H292 cells (2.8-fold increase in damage index compared to the negative control), but not in PBMC. CONCLUSION: Compound 5 presented selective cytotoxic and genotoxic activity against pulmonary carcinoma (NCI-H292 cells).
Assuntos
Antineoplásicos/farmacologia , Citotoxinas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Mutagênicos/farmacologia , Tiazolidinedionas/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Ensaio Cometa/métodos , Fragmentação do DNA/efeitos dos fármacos , Células HL-60 , Humanos , Células K562 , Leucócitos Mononucleares/efeitos dos fármacos , Células MCF-7RESUMO
A series of arylamidines 3a-j was designed, synthesized and investigated for antimicrobial activity. Structures of the compounds were confirmed by IR, 1H-NMR and 13C-NMR and a 2D spectroscopic study was performed. A preliminary screening of the antimicrobial tests clearly showed that three out of ten arylamidines, viz, 3f, 3g and 3i, were effective against all the gram-negative bacteria: Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella enteric; and against the yeast, candida albicans. Further, the Minimum Inhibitory Concentrations (MIC) against the bacteria and yeast were determined. All compounds 3a-d, 3f, 3g, 3i and 3j were also investigated for their low cytotoxic effects on tested cell lines. Compounds 3d and 3f were the most effective derivatives against HL-60 and HEp-2 cells, respectively, with IC50 value (2µg/mL), and low normal cells toxicity.
Assuntos
Amidinas/síntese química , Amidinas/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Candida albicans/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Teste de Materiais , Testes de Sensibilidade Microbiana , Reprodutibilidade dos Testes , Espectrofotometria Infravermelho , Sais de Tetrazólio , Tiazóis , Testes de ToxicidadeRESUMO
ABSTRACT A series of arylamidines 3a-j was designed, synthesized and investigated for antimicrobial activity. Structures of the compounds were confirmed by IR, 1H-NMR and 13C-NMR and a 2D spectroscopic study was performed. A preliminary screening of the antimicrobial tests clearly showed that three out of ten arylamidines, viz, 3f, 3g and 3i, were effective against all the gram-negative bacteria: Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella enteric; and against the yeast, candida albicans. Further, the Minimum Inhibitory Concentrations (MIC) against the bacteria and yeast were determined. All compounds 3a-d, 3f, 3g, 3i and 3j were also investigated for their low cytotoxic effects on tested cell lines. Compounds 3d and 3f were the most effective derivatives against HL-60 and HEp-2 cells, respectively, with IC50 value (2µg/mL), and low normal cells toxicity.