Abstract
Acridine derivatives represent a well-known class of anticancer agents that generally interfere with DNA synthesis and inhibit topoisomerase II. A series of eight new 3-acridin-9-ylmethyl-thiazolidine-2,4-dione and 3-acridin-9-ylmethyl-5-arylidene-thiazolidine-2,4-dione derivatives were synthesized. All the compounds were evaluated for their cell antiproliferation activity with the 3-(4,5-dimethyl-2-thiozolyl)-2,5-diphenyl-2H-tetrazolium bromide, MTT assay. The antiproliferative effects of the synthesized compounds were tested against several tumoral cell lines, namely SF-295 (central nervous system), HCT-8 (colon carcinoma), and MDA-MB-435 (melanoma) cells using doxorubicin as a positive control. Among the synthesized compounds, 3-acridin-9-ylmethyl-5-acridin-9-ylmethylene-thiazolidine-2,4-dione, 3-acridin-9-ylmethyl-5-(4-methoxy-benzylidene)-thiazolidine-2,4-dione, and 3-acridin-9-ylmethyl-5-(4-bromo-benzylidene)-thiazolidine-2,4-dione exhibited the most potent anticancer activity against the HCT-8 and MDA-MB-435 cell lines. After a detailed analysis of the structure of the thiazacridine molecules, we revealed the main possible interactions using the compound 3-acridin-9-ylmethyl-5-acridin-9-ylmethylene-thiazolidine-2,4-dione as an example. The benefits of these compounds, regardless of the pharmacological target are the presence of two aromatic rings (pi systems), significant planarity (intercalating ability) and the presence of three hydrogen-bond acceptors, two of which are stronger (oxygen atoms) than the other (sulfur atom).
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Acknowledgments
The authors are thankful to CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brasil), the CAPES/COFECUB (Fundação Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior/Comité Français d’Evaluation de la Coopération Universitaire avec le Brésil), the INCT_IF (Instituto Nacional de Ciência e Tecnologia para Inovação Farmacêutica) and the PPGIT (Programa de Pós-Graduação em Inovação Terapêutica) for their support of the joint research program.
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da Rocha Pitta, M.G., Souza, É.S., Barros, F.W.A. et al. Synthesis and in vitro anticancer activity of novel thiazacridine derivatives. Med Chem Res 22, 2421–2429 (2013). https://doi.org/10.1007/s00044-012-0236-2
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DOI: https://doi.org/10.1007/s00044-012-0236-2