Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine Derivatives
| Autor: | Marina Galdino da Rocha Pitta, Ricardo Olímpio de Moura, Teresinha Gonçalves da Silva, Ivan da Rocha Pitta, Elizabeth Almeida Lafayette, Eduardo Isidoro Carneiro Beltrão, Sinara Mônica Vitalino de Almeida, Luiz Bezerra de Carvalho, Maria do Carmo Alves de Lima |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Circular dichroism
Stereochemistry Intercalation (chemistry) imidazacridine Pharmaceutical Science Antineoplastic Agents Topoisomerase-I Inhibitor Article Fluorescence spectroscopy Analytical Chemistry lcsh:QD241-441 chemistry.chemical_compound lcsh:Organic chemistry Drug Discovery medicine Humans topoisomerase I inhibitor Physical and Theoretical Chemistry DNA binding Molecular Structure biology Circular Dichroism Topoisomerase thiazacridine Organic Chemistry DNA Fluorescence Enzyme Activation DNA Topoisomerases Type I Mechanism of action chemistry Chemistry (miscellaneous) biology.protein Acridines Molecular Medicine Topoisomerase I Inhibitors medicine.symptom |
| Zdroj: | Molecules, Vol 18, Iss 12, Pp 15035-15050 (2013) Molecules; Volume 18; Issue 12; Pages: 15035-15050 Molecules |
| ISSN: | 1420-3049 |
| Popis: | 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 × 10(4) to 6.01 × 10(4) 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. |
| Databáze: | OpenAIRE |
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