New fluorescent antitumour cisplatin analogue complexes. Study of the characteristics of their binding to DNA by flow injection analysis.
The flow injection technique is applied to study the binding to DNA of new platinum complexes-E(1): ethylenediaminechlorocholylglycinateplatinum(II): [PtCl(CG)(en)], C(54)H(92)O(12)Pt and E(2): ethylenediaminebischolylglycinateplatinum(II): [Pt(CG)(2)(en)], C(28)H(50)ClN(3)O(6)Pt-derived from cisplatin in which the exchangeable ligands were replaced by bile acids, such that these anticancer drugs have less toxicity and less resistance is developed towards them. Both compounds are fluorescent and their fluorescence is enhanced when they form adducts with DNA, a property that is extremely useful for monitoring the cytotoxic activity and their mechanisms of action. The binding parameters to DNA of E(1) [apparent intrinsic binding constant K(E1): (11.2 +/- 0.4) x 10(3) M(-1) and maximum number of binding sites per nucleotide, n (E1): 0.121 +/- 2 x 10(-3)) and E(2) (K(E2): 9.2 +/- 0.7) x 10(3) M(-1) and n (E2) 0.098 +/- 2 x 10(-3)] were determined following the Scatchard method and the type of binding was studied experimentally through the modifications introduced by each of the compounds into the ethidium bromide-DNA bond.
Alonso
A
A
Departamento de Química Analítica, Nutrición y Bromatología, Faculty of Chemistry, University of Salamanca, Plaza de la Merced s/n, 37008 Salamanca, Spain.
Almendral
M J
MJ
Curto
Y
Y
Criado
J J
JJ
Rodríguez
E
E
Manzano
J L
JL
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D017022:Flow Injection Analysis; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D046911:Macromolecular Substances; D013050:Spectrometry, Fluorescence
D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D046911:Macromolecular Substances; D004247:DNA; D002945:Cisplatin