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Correlation between DNA/HSA-interactions and antimalarial activity of acridine derivatives: Proposing a possible mechanism of action

de M. Silva, Marina ; Macedo, Taís S. ; Teixeira, Helena Mariana P. ; Moreira, Diogo Rodrigo M. ; Soares, Milena B.P. ; da C. Pereira, Ana Ligia ; de L. Serafim, Vanessa ; Mendonça-Júnior, Francisco J.B. ; do Carmo A. de Lima, Maria ; de Moura, Ricardo O. ; da Silva-Júnior, Edeildo F. ; de Araújo-Júnior, João Xavier ; de A. Dantas, Maria Dayanne ; de O. O. Nascimento, Eduarda ; Maciel, Thamilla Maria S. ; de Aquino, Thiago Mendonça ; Figueiredo, Isis M. ; Santos, Josué C.C.

Journal of photochemistry and photobiology. B, Biology, 2018-12, Vol.189, p.165-175 [Periódico revisado por pares]

Switzerland: Elsevier B.V

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Título:
Correlation between DNA/HSA-interactions and antimalarial activity of acridine derivatives: Proposing a possible mechanism of action
Autor: de M. Silva, Marina ; Macedo, Taís S. ; Teixeira, Helena Mariana P. ; Moreira, Diogo Rodrigo M. ; Soares, Milena B.P. ; da C. Pereira, Ana Ligia ; de L. Serafim, Vanessa ; Mendonça-Júnior, Francisco J.B. ; do Carmo A. de Lima, Maria ; de Moura, Ricardo O. ; da Silva-Júnior, Edeildo F. ; de Araújo-Júnior, João Xavier ; de A. Dantas, Maria Dayanne ; de O. O. Nascimento, Eduarda ; Maciel, Thamilla Maria S. ; de Aquino, Thiago Mendonça ; Figueiredo, Isis M. ; Santos, Josué C.C.
Assuntos: Acridine ; Acridines ; Acridines - chemical synthesis ; Acridines - pharmacology ; Activity-interaction correlation ; Antimalarial activity ; Antimalarial agents ; Antimalarials - pharmacology ; Antimicrobial agents ; Binding ; Binding Sites ; Biological activity ; Calf thymus DNA and HSA interaction ; Complex formation ; Coordination compounds ; Deoxyribonucleic acid ; Derivatives ; DNA ; DNA - metabolism ; Energy transfer ; Fluorescence ; Humans ; Intercalating Agents - pharmacology ; Molecular docking ; Photochemistry ; Plasmodium falciparum ; Primaquine ; Protein Binding ; Proteins ; Serum Albumin, Human - metabolism ; Structure-Activity Relationship
É parte de: Journal of photochemistry and photobiology. B, Biology, 2018-12, Vol.189, p.165-175
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: 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. [Display omitted] •Acridine 2 was more effective against P. falciparum than primaquine.•The preferential binding mode of acridines with DNA was by intercalation.•The acridines derivatives evaluated preferentially binding in the site II of the HSA.•Correlation between Kb and IC50 suggests that DNA is a possible biological target.•The acridine-DNA affinity in vitro conditions following the order: 2 > 4 > 1 > 3.
Editor: Switzerland: Elsevier B.V
Idioma: Inglês

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Correlation between DNA/HSA-interactions and antimalarial activity of acridine derivatives: Proposing a possible mechanism of action

Switzerland: Elsevier B.V

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