Mononuclear copper(II) complexes with 2-thiophene carboxylate and N-N donors; DNA interaction, antioxidant/anti-inflammatory and antitumor activity.
Mater Sci Eng C Mater Biol Appl
; 94: 493-508, 2019 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-30423734
ABSTRACT
Redox-active compounds such as copper-phenanthroline are known as artificial/chemical nucleases with a great impact and potential for their applications as metallotherapeutics. In that vein, the mononuclear copper(II) complexes [Cu(L)2(bipy)] (1), [Cu(L)2(bipy)(H2O)] (2) and [Cu(L)2(phen)(H2O)] (3), where Lâ¯=â¯2-thiophene carboxylate, bipyâ¯=â¯2,2Î-bipyridine and phenâ¯=â¯1,10-phenanthroline, have been prepared and pharmacochemically studied, while the crystal structure of 1 is also reported. All the tested complexes preferably bind to CT-DNA via minor groove as resulted from UV spectroscopy studies, luminescent titration, EB competition assays and viscosity measurements. Complexes 2 and 3 in aqua behave like a "light switch" for DNA. The intensity enhancement, with the increase of DNA concentration, reached about 3-fold for 2 and 10-fold for 3. In vitro antioxidant activity of compounds 1-3, was evaluated using two different antioxidant assays a) interaction with 1,1-diphenyl-2-picryl-hydrazyl (DPPH) stable free radical and b) inhibition of lipid peroxidation. Moreover, their inhibitory activity on soybean lipoxygenase (LOX) was evaluated for their anti-inflammatory potency. The tested complexes showed good activity on both lipid peroxidation and soybean LOX inhibition while complex 2 exhibited the best antioxidant/anti-inflammatory activity. A computational analysis over the LOX protein structure 1JNQ was performed, in an effort to support their possible mode of action. The cytotoxicity of the complexes was determined and their efficacy against several human cancer cell lines (ovarian, OAW-42; lung, A549; colon, HT29; breast, MDA-MB-231; kidney, Caki-2; and cervical, Hela) and human non-tumor cell lines (lung, MRC-5; and breast, MTSV1-7) were evaluated. The best cytotoxic activity was appeared for complex 3. In silico, computational methods support antiestrogen activity of the administered complexes on normal breast cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiofenos
/
DNA
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Ácidos Carboxílicos
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Cobre
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Anti-Inflamatórios
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Antineoplásicos
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Antioxidantes
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mater Sci Eng C Mater Biol Appl
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Grécia