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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Published in:Molecules (Basel, Switzerland) Switzerland), 2013-12, Vol.18 (12), p.15035-15050
Main Authors: Lafayette, Elizabeth Almeida, Vitalino de Almeida, Sinara Mônica, Pitta, Marina Galdino da Rocha, Carneiro Beltrão, Eduardo Isidoro, da Silva, Teresinha Gonçalves, Olímpio de Moura, Ricardo, Pitta, Ivan da Rocha, de Carvalho, Jr, Luiz Bezerra, de Lima, Maria do Carmo Alves
Format: Article
Language:English
Subjects:
Acridines - chemical synthesis
Acridines - metabolism
Acridines - pharmacology
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Apoptosis
Cancer therapies
Circular Dichroism
DNA - chemistry
DNA - metabolism
DNA binding
DNA Topoisomerases, Type I - metabolism
Drugs
Electronic mail systems
Enzyme Activation - drug effects
Humans
imidazacridine
Molecular Structure
thiazacridine
topoisomerase I inhibitor
Topoisomerase I Inhibitors - chemical synthesis
Topoisomerase I Inhibitors - metabolism
Topoisomerase I Inhibitors - pharmacology
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Summary: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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules181215035