title: ACMA (9-amino-6-chloro-2-methoxy acridine) forms three complexes in the presence of DNA.
abstract: The interaction of ACMA (9-amino-6-chloro-2-methoxy acridine) (D) with DNA (P) has been studied by absorbance, fluorescence, circular dichroism, spectrophotometry, viscometry and unwinding electrophoresis. A T-jump kinetic study has also been undertaken. The experimental data show that, totally unlike other drugs, ACMA is able to form with DNA three complexes (PD(I), PD(II), PD(III)) that differ from each other by the characteristics and extent of the binding process. The main features of PD(I) fulfil the classical intercalation pattern and the formation/dissociation kinetics have been elucidated by T-jump techniques. PD(II) and PD(III) are also intercalated species but, in addition to the dye units lodged between base pairs, they also bear dye molecules externally bound, more in PD(III) relative to PD(II). A reaction mechanism is put forward here. Comparison between absorbance, fluorescence and kinetic experiments has enabled us to determine the binding constants of the three complexes, namely (6.5 ± 1.1) × 10(4) M(-1) (PD(I)), (5.5 ± 1.5) × 10(4) M(-1) (PD(II)) and (5.7 ± 0.03) × 10(4) M(-1) (PD(III)). The Comet assay reveals that the ACMA binding to DNA brings about genotoxic properties. The mutagenic potential studied by the Ames test reveals that ACMA can produce frameshift and transversion/transition mutations. ACMA also is able to produce base-pair substitution in the presence of S9 mix. Moreover, the MTT assays have revealed cytotoxicity. The biological effects observed have been rationalized in light of these features.
authors.affiliation: Universidad de Burgos, Departamento de Química, 09001 Burgos, Spain. nataliabyv@msn.com
authors.forename: Natalia
authors.initials: N
authors.lastname: Busto
authors.forename: Begoña
authors.initials: B
authors.lastname: García
authors.forename: José M
authors.initials: JM
authors.lastname: Leal
authors.forename: Jorge F
authors.initials: JF
authors.lastname: Gaspar
authors.forename: Célia
authors.initials: C
authors.lastname: Martins
authors.forename: Alessia
authors.initials: A
authors.lastname: Boggioni
authors.forename: Fernando
authors.initials: F
authors.lastname: Secco
mesh_terms: D000609:Aminoacridines / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D013053:Spectrophotometry; D013816:Thermodynamics
chemical_list: D000609:Aminoacridines; D056831:Coordination Complexes; C010847:9-amino-6-chloro-2-methoxyacridine; D010165:Palladium; D004247:DNA