Inhibition of DNA topoisomerases I and II and growth inhibition of HL-60 cells by novel acridine-based compounds.
Eur J Pharm Sci
; 76: 192-202, 2015 Aug 30.
Article
en En
| MEDLINE
| ID: mdl-25960253
ABSTRACT
HL-60 cancer cells were treated with a series of novel acridine derivatives (derivatives 1-4) in order to test the compounds' ability to inhibit both cancer cell growth and topoisomerase I and II activity. Binding studies of derivatives 1-4 with calf thymus DNA were also performed using a number of techniques (UV-Vis and fluorescence spectroscopy, thermal denaturation, linear dichroism and viscometry) to determine the nature of the interaction between the compounds and ctDNA. The binding constants for the complexes of the studied acridine derivatives with DNA were calculated from UV-Vis spectroscopic titrations (K=3.1×10(4)-2.0×10(3)M(-1)). Some of the compounds showed a strong inhibitory effect against Topo II at the relatively low concentration of 5µM. Topo I/II inhibition mode assays were also performed and verified that the novel compounds are topoisomerase suppressors rather than poisons. The biological activities of derivatives were studied using MTT assay and flow cytometric methods (detection of mitochondrial membrane potential, measurement of cell viability) after 24 and 48h incubation. The ability of derivatives to impair cell proliferation was tested by an analysis of cell cycle distribution.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Acridinas
/
Leucemia Promielocítica Aguda
/
ADN-Topoisomerasas de Tipo II
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ADN-Topoisomerasas de Tipo I
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Proliferación Celular
/
Inhibidores de Topoisomerasa I
/
Inhibidores de Topoisomerasa II
Límite:
Humans
Idioma:
En
Revista:
Eur J Pharm Sci
Asunto de la revista:
FARMACIA
/
FARMACOLOGIA
/
QUIMICA
Año:
2015
Tipo del documento:
Article