Selective cytotoxic and genotoxic activities of 5-(2-bromo-5-methoxybenzylidene)-thiazolidine-2,4-dione against NCI-H292 human lung carcinoma cells

dc.creatorRodrigues, Maria do D.
dc.creatorSantiago, Priscila B. G. S.
dc.creatorMarques, Karla M. R.
dc.creatorPereira, Valéria R. A.
dc.creatorCastro, Maria C. A. B. de
dc.creatorCantalice, Jeanne C. L. L.
dc.creatorSilva, Teresinha G. da
dc.creatorAdam, Mônica L.
dc.creatorNascimento, Silene C. do
dc.creatorAlbuquerque, Julianna F. C. de
dc.creatorMilitao, Gardenia C. G.
dc.date2019-05-06T13:17:23Z
dc.date2019-05-06T13:17:23Z
dc.date2018
dc.date.accessioned2023-09-27T00:09:17Z
dc.date.available2023-09-27T00:09:17Z
dc.identifierRODRIGUES, M. do D. et al. Selective cytotoxic and genotoxic activities of 5-(2-bromo-5-methoxybenzylidene)-thiazolidine-2,4-dione against NCI-H292 human lung carcinoma cells. Pharmacological Reports, v. 70, n. 3, p. 446–454, 1 jun. 2018.
dc.identifier1734-1140
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/32942
dc.identifier10.1016/j.pharep.2017.11.008
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8897979
dc.descriptionCNPq e FACEPE.
dc.descriptionBACKGROUND: 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).
dc.formatapplication/pdf
dc.languageeng
dc.rightsopen access
dc.subjectCytotoxicity
dc.subjectGenotoxicity
dc.subject5-Benzylidene-2,4-thiazolidinedione
dc.subjectLungcancer
dc.subjectAntineoplásicos / farmacologia
dc.subjectApoptose / efeitos de drogas
dc.subjectLinha Celular, Tumor
dc.subjectEnsaio Cometa / métodos
dc.subjectCitotoxinas / farmacologia
dc.subjectFragmentação de DNA / efeitos de drogas
dc.subjectCélulas HL-60
dc.subjectHumanos
dc.subjectCélulas K562
dc.subjectLeucócitos Mononucleares / efeitos de drogas
dc.subjectNeoplasias Pulmonares / quimioterapia
dc.subjectCélulas MCF-7
dc.subjectMutagénicos / farmacologia
dc.subjectTiazolidinedionas / farmacologia
dc.titleSelective cytotoxic and genotoxic activities of 5-(2-bromo-5-methoxybenzylidene)-thiazolidine-2,4-dione against NCI-H292 human lung carcinoma cells
dc.typeArticle


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