Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine Derivatives
by
Elizabeth Almeida Lafayette 1, Sinara Mônica Vitalino de Almeida 2,3, Marina Galdino Da Rocha Pitta 1, Eduardo Isidoro Carneiro Beltrão 2, Teresinha Gonçalves da Silva 4, Ricardo Olímpio de Moura 5, Ivan Da Rocha Pitta 1, Luiz Bezerra De Carvalho, Júnior 2 and Maria Do Carmo Alves de Lima 1,*
Elizabeth Almeida Lafayette 1, Sinara Mônica Vitalino de Almeida 2,3, Marina Galdino Da Rocha Pitta 1, Eduardo Isidoro Carneiro Beltrão 2, Teresinha Gonçalves da Silva 4, Ricardo Olímpio de Moura 5, Ivan Da Rocha Pitta 1, Luiz Bezerra De Carvalho, Júnior 2 and Maria Do Carmo Alves de Lima 1,*
1
Laboratório de Planejamento e Síntese de Fármacos, Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, Brazil
2
Laboratório de Imunopatologia Keizo Asami (LIKA) and Departamento de Bioquímica, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, Brazil
3
Faculdade de Ciências, Educação e Tecnologia de Garanhuns (FACETEG), Universidade de Pernambuco (UPE), Garanhuns 55290-000, PE, Brazil
4
Laboratório de Bioensaios para Pesquisa de Fármacos, Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, Brazil
5
Universidade Estadual da Paraíba (UEPB), Campus Campina Grande 58429-500, PB, Brazil
*
Author to whom correspondence should be addressed.
Molecules 2013, 18(12), 15035-15050; https://doi.org/10.3390/molecules181215035
Received: 22 September 2013 / Revised: 27 November 2013 / Accepted: 2 December 2013 / Published: 6 December 2013
(This article belongs to the Section Medicinal Chemistry)
Thiazacridine and imidazacridine derivatives have shown promising results as tumors suppressors in some cancer cell lines. For a better understanding of the mechanism of action of these compounds, binding studies of 5-acridin-9-ylmethylidene-3-amino-2-thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2-thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2-thioxo-imidazolidin-4-one and 3-acridin-9-ylmethyl-thiazolidin-2,4-dione with calf thymus DNA (ctDNA) by electronic absorption and fluorescence spectroscopy and circular dichroism spectroscopy were performed. The binding constants ranged from 1.46 × 104 to 6.01 × 104 M−1. UV-Vis, fluorescence and circular dichroism measurements indicated that the compounds interact effectively with ctDNA, both by intercalation or external binding. They demonstrated inhibitory activities to human topoisomerase I, except for 5-acridin-9-ylmethylidene-2-thioxo-1,3-thiazolidin-4-one. These results provide insight into the DNA binding mechanism of imidazacridines and thiazacridines.
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Keywords:
thiazacridine; imidazacridine; DNA binding; topoisomerase I inhibitor
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MDPI and ACS Style
Lafayette, E.A.; Vitalino de Almeida, S.M.; Da Rocha Pitta, M.G.; Carneiro Beltrão, E.I.; Gonçalves da Silva, T.; Olímpio de Moura, R.; Da Rocha Pitta, I.; De Carvalho, L.B., Júnior; Do Carmo Alves de Lima, M. Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine Derivatives. Molecules 2013, 18, 15035-15050.
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