Article
Correlation between DNA/HSA-interactions and antimalarial activity of acridine derivatives: Proposing a possible mechanism of action
Registro en:
SILVA, M. M. et al. Correlation between DNA/HSA-interactions and antimalarial activity of acridine derivatives: Proposing a possible mechanism of action. Journal of Photochemistry and Photobiology B: Biology, v. 189, p. 165-175, 2018.
1011-1344
10.1016/j.jphotobiol.2018.10.016
Autor
Silva, Marina de Magalhães
Macedo, Taís Soares
Teixeira, Helena Mariana Pitangueira
Moreira, Diogo Rodrigo de Magalhaes
Soares, Milena Botelho Pereira
Pereira, Ana Ligia da Costa
Serafim, Vanessa de Lima
Mendonça Júnior, Francisco Jaime Bezerra
Lima, Maria do Carmo Alves de
Moura, Ricardo Olímpio de
Silva Júnior, Edeildo Ferreira da
Araújo Júnior, João Xavier de
Dantas, Maria Dayanne de Araujo
Nascimento, Eduarda de Omena Oliveira
Maciel, Thamilla Maria Silva
Aquino, Thiago Mendonça de
Figueiredo, Isis Martins
Santos, Josué Carinhanha Caldas
Resumen
Instituto de Química e Biotecnologia
(UFAL), Conselho Nacional de Desenvolvimento Científico e
Tecnológico (CNPq), FAPEAL (Process number 60030 000863/2016),
FAPESB, FAPESQ and FACEPE. This study was financed in part by the
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil
(CAPES) - Finance Code 001. Acridines are considered an important class of compounds due to their wide variety of biological activities. In this work, we synthesized four acridine derivatives (1-4) and evaluated their biological activity against the Plasmodium falciparum W2 line, as well as studied the interaction with ctDNA and HSA using spectroscopic techniques and molecular docking. The acridine derivative 2 (IC50 = 0.90 ± 0.08 μM) was more effective against P. falciparum than primaquine (IC50 = 1.70 ± 0.10 μM) and similar to amsacrine (IC50 = 0.80 ± 0.10 μM). In the fluorescence and UV-vis assays, it was verified that the acridine derivatives interact with ctDNA and HSA leading to a non-fluorescent supramolecular complex formation. The non-covalent binding constants ranged from 2.09 to 7.76 × 103 M-1, indicating moderate interaction with ctDNA. Through experiments with KI, fluorescence contact energy transfer and competition assays were possible to characterize the main non-covalent binding mode of the acridines evaluated with ctDNA as intercalation. The binding constants obtained showed a high linear correlation with the IC50 values against the antimalarial activity, suggesting that DNA may be the main biological target of these molecules. Finally, HSA interaction studies were performed and all evaluated compounds bind to the site II of the protein. The less active compounds (1 and 3) presented the highest affinity to HSA, indicating that the interaction with carrier protein can affect the (bio)availability of these compounds to the biological target.