NDLI: Mixed-ligand copper(II)–sulfonamide complexes: effect of the sulfonamide derivative on DNA binding, DNA cleavage, genotoxicity and anticancer activity

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Mixed-ligand copper(II)–sulfonamide complexes: effect of the sulfonamide derivative on DNA binding, DNA cleavage, genotoxicity and anticancer activity

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Alzuet-piña, Gloria Castiñeiras, Alfonso Del Castillo Agudo, Lucas Borrás, Joaquín González-álvarez, Marta Liu-gonzález, Malva Pascual-álvarez, Alejandro
Description	Author Affiliation: González-Álvarez M ( Departament de Química Inorgànica, Facultat de Farmàcia, Universitat de València, Avda. Vicent Andrés Estellés s/n, 46100-Burjassot, Spain.)
Abstract	Four ternary complexes, $[Cu(L1)_{2}(bipy)]$ (1) [HL1 = N-(6-chlorobenzo[d]thiazol-2-yl)-4-methylbenzenesulfonamide], $[Cu(L2)_{2}(bipy)]$ (2) [HL2 = N-(benzo[d]thiazol-2-yl)-4-methylbenzenesulfonamide], $[Cu(L3)_{2}(bipy)]·1/2H_{2}O$ (3) [HL3 = N-(5,6-dimethylbenzo[d]thiazol-2-yl)-4-methylbenzenesulfonamide] and $[Cu(L4)_{2}(bipy)]$ (4) [HL4 = N-(5,6-dimethylbenzo[d]thiazol-2-yl)benzenesulfonamide], were prepared and then characterized by X-ray crystallography, spectroscopy and magnetic measurements. Whereas the molecular structure of 1 and 2 consists of a discrete monomeric copper(II) species with a distorted square planar geometry, that of 3 and 4 consists of two independent molecules. In 3, both molecules present a different coordination geometry (distorted square planar and distorted square pyramidal) while in 4 they have an identical coordination environment (distorted square planar). The propensity for binding of 1–4 to calf thymus DNA was studied by thermal denaturation, viscosimetry, and fluorescence measurements. Results indicated that the N-sulfonamide derivative plays an important role in governing the type of interaction with DNA. The ability of the complexes to cleave DNA was studied in vitro with ascorbate activation and was tested by monitoring the expression of the yEGFP gene containing the RAD54 reporter. Moreover, their antiproliferative activity was verified in two cellular models: yeast and human tumor cells in culture. Their DNA cleavage efficiency at the cellular level was found to be: 1 < 3 ∼ 4 < 2. The higher propensity of 2 for inflicting DNA damage was related with its higher binding affinity to DNA. The biological studies carried out with human tumor cells, colon adenocarcinoma Caco-2 cells and leukemia Jurkat T lymphocytes confirmed that the compounds produce cell death mainly by apoptosis, the complex 2 being the most effective.
ISSN	14779226
Issue Number	28
Volume Number	42
e-ISSN	13645447
Journal	Dalton Trans.
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2013-07-28
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Antineoplastic Agents Chemistry Coordination Complexes Copper Sulfonamides Pharmacology Apoptosis Drug Effects Caco-2 Cells Cell Proliferation Cell Survival DNA DNA Cleavage Humans Jurkat Cells Ligands Saccharomyces Cerevisiae Journal Article Research Support, Non-U.S. Gov't
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

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