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Molecules 2013, 18(12), 15035-15050; doi:10.3390/molecules181215035
Article

Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine Derivatives

1
, 2,3
, 1
, 2
, 4
, 5
, 1
, Júnior 2
 and 1,*
Received: 22 September 2013; in revised form: 27 November 2013 / Accepted: 2 December 2013 / Published: 6 December 2013
(This article belongs to the Section Medicinal Chemistry)
Download PDF [693 KB, uploaded 18 June 2014]
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 × 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.
Keywords: thiazacridine; imidazacridine; DNA binding; topoisomerase I inhibitor thiazacridine; imidazacridine; DNA binding; topoisomerase I inhibitor
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

AMA Style

Lafayette EA, Vitalino de Almeida SM, da Rocha Pitta MG, Carneiro Beltrão EI, Gonçalves da Silva T, Olímpio de Moura R, da Rocha Pitta I, de Carvalho LB, Júnior, do Carmo Alves de Lima M. Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine Derivatives. Molecules. 2013; 18(12):15035-15050.

Chicago/Turabian Style

Lafayette, Elizabeth A.; Vitalino de Almeida, Sinara M.; da Rocha Pitta, Marina G.; Carneiro Beltrão, Eduardo I.; Gonçalves da Silva, Teresinha; Olímpio de Moura, Ricardo; da Rocha Pitta, Ivan; de Carvalho, Luiz B., Júnior; do Carmo Alves de Lima, Maria. 2013. "Synthesis, DNA Binding and Topoisomerase I Inhibition Activity of Thiazacridine and Imidazacridine Derivatives." Molecules 18, no. 12: 15035-15050.


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