Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine Derivatives
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-ylmethylid...
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| Format: | Article |
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MDPI AG
2013-12-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/18/12/15035 |
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| author | Elizabeth Almeida Lafayette Sinara Mônica Vitalino de Almeida Marina Galdino da Rocha Pitta Eduardo Isidoro Carneiro Beltrão Teresinha Gonçalves da Silva Ricardo Olímpio de Moura Ivan da Rocha Pitta Luiz Bezerra de Carvalho Maria do Carmo Alves de Lima |
| author_facet | Elizabeth Almeida Lafayette Sinara Mônica Vitalino de Almeida Marina Galdino da Rocha Pitta Eduardo Isidoro Carneiro Beltrão Teresinha Gonçalves da Silva Ricardo Olímpio de Moura Ivan da Rocha Pitta Luiz Bezerra de Carvalho Maria do Carmo Alves de Lima |
| author_sort | Elizabeth Almeida Lafayette |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T18:18:36Z |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-11T18:18:36Z |
| publishDate | 2013-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-0429fba2111540dfab4ef395fa284c432022-12-22T00:55:20ZengMDPI AGMolecules1420-30492013-12-011812150351505010.3390/molecules181215035molecules181215035Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine DerivativesElizabeth Almeida Lafayette0Sinara Mônica Vitalino de Almeida1Marina Galdino da Rocha Pitta2Eduardo Isidoro Carneiro Beltrão3Teresinha Gonçalves da Silva4Ricardo Olímpio de Moura5Ivan da Rocha Pitta6Luiz Bezerra de Carvalho7Maria do Carmo Alves de Lima8Laboratório de Planejamento e Síntese de Fármacos, Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, BrazilLaboratório de Imunopatologia Keizo Asami (LIKA) and Departamento de Bioquímica, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, BrazilLaboratório de Planejamento e Síntese de Fármacos, Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, BrazilLaboratório de Imunopatologia Keizo Asami (LIKA) and Departamento de Bioquímica, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, BrazilLaboratório de Bioensaios para Pesquisa de Fármacos, Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, BrazilUniversidade Estadual da Paraíba (UEPB), Campus Campina Grande 58429-500, PB, BrazilLaboratório de Planejamento e Síntese de Fármacos, Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, BrazilLaboratório de Imunopatologia Keizo Asami (LIKA) and Departamento de Bioquímica, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, BrazilLaboratório de Planejamento e Síntese de Fármacos, Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, BrazilThiazacridine 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.http://www.mdpi.com/1420-3049/18/12/15035thiazacridineimidazacridineDNA bindingtopoisomerase I inhibitor |
| spellingShingle | Elizabeth Almeida Lafayette Sinara Mônica Vitalino de Almeida Marina Galdino da Rocha Pitta Eduardo Isidoro Carneiro Beltrão Teresinha Gonçalves da Silva Ricardo Olímpio de Moura Ivan da Rocha Pitta Luiz Bezerra de Carvalho Maria do Carmo Alves de Lima Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine Derivatives Molecules thiazacridine imidazacridine DNA binding topoisomerase I inhibitor |
| title | Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine Derivatives |
| title_full | Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine Derivatives |
| title_fullStr | Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine Derivatives |
| title_full_unstemmed | Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine Derivatives |
| title_short | Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine Derivatives |
| title_sort | synthesis dna binding and topoisomerase i inhibition activity of thiazacridine and imidazacridine derivatives |
| topic | thiazacridine imidazacridine DNA binding topoisomerase I inhibitor |
| url | http://www.mdpi.com/1420-3049/18/12/15035 |
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