1. Synthesis, DNA binding and topoisomerase I inhibition activity of thiazacridine and imidazacridine derivatives.
- Author
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Lafayette EA, Vitalino de Almeida SM, Pitta MG, Carneiro Beltrão EI, da Silva TG, Olímpio de Moura R, Pitta Ida R, de Carvalho LB Jr, and de Lima Mdo C
- Subjects
- Acridines metabolism, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Circular Dichroism, DNA chemistry, DNA metabolism, DNA Topoisomerases, Type I metabolism, Enzyme Activation drug effects, Humans, Molecular Structure, Topoisomerase I Inhibitors metabolism, Acridines chemical synthesis, Acridines pharmacology, Topoisomerase I Inhibitors chemical synthesis, Topoisomerase I Inhibitors pharmacology
- Abstract
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.
- Published
- 2013
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