Internet Archive Scholar

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

Maria do D. Rodrigues, Priscila B.G.S. Santiago, Karla M.R. Marques, Valéria R.A. Pereira, Maria C.A.B. de Castro, Jeanne C.L.L. Cantalice, Teresinha G. da Silva, Mônica L. Adam, Silene C. do Nascimento, Julianna F.C. de Albuquerque, Gardenia C.G. Militao
2018 Pharmacological Reports  

Preserved Fulltext

fulltext thumbnail
Web Archive Capture PDF (3.1 MB)
https://web.archive.org/web/20200309083348/https://www.arca.fiocruz.br/bitstream/icict/32942/2/1-s2.0-S1734114017300610-main.pdf

A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2020; you can also visit the original URL. The file type is application/pdf.

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-2,4thiazolidinedione 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
more » ... a), 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 IC 50 value of 1.26 mg/mL after 72 h incubation. None of the compounds were cytotoxic to PBMC. After 48 h 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).
doi:10.1016/j.pharep.2017.11.008 pmid:29627691 fatcat:bxsldixsyjf5vpvi7pkzi5ufxe
Open Access
Citation

Maria do D. Rodrigues, Priscila B.G.S. Santiago, Karla M.R. Marques, Valéria R.A. Pereira, Maria C.A.B. de Castro, Jeanne C.L.L. Cantalice, Teresinha G. da Silva, Mônica L. Adam, Silene C. do Nascimento, Julianna F.C. de Albuquerque, Gardenia C.G. Militao. "Selective cytotoxic and genotoxic activities of 5-(2-bromo-5-methoxybenzylidene)-thiazolidine-2,4-dione against NCI-H292 human lung carcinoma cells." Pharmacological Reports 70.3 (2018) 446-454