RESUMO
A series of new mixed-ligand neutral copper(II) complexes of the general type [Cu(amine)(i-MNT)] and [Cu(tz)(i-MNT)] was prepared and characterized by elemental, spectroscopic methods, mu(eff), Lambda(mu) measurements and molecular modeling studies. The acute toxicity, the cytogenetic and the in vivo antitumor activity of the new complexes, is related to their chemical and physicochemical properties. Among the Cu(II) compounds tested the complex with 2-amino-5-methyl thiazole increases significantly the life span of leukemia P388 bearing mice in vivo.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Cobre/química , Compostos Organometálicos/síntese química , Compostos Organometálicos/farmacologia , Aminas/síntese química , Aminas/química , Aminas/farmacologia , Animais , Antineoplásicos/síntese química , Feminino , Humanos , Leucemia P388/tratamento farmacológico , Ligantes , Linfócitos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Modelos Moleculares , Compostos Organometálicos/química , Troca de Cromátide Irmã/efeitos dos fármacos , Espectrofotometria Infravermelho , Relação Estrutura-Atividade , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/química , Compostos de Sulfidrila/farmacologia , Tiazóis/síntese química , Tiazóis/química , Tiazóis/farmacologiaRESUMO
Highly reactive radicals are implicated in many pathological conditions. The quest for radical scavengers or antioxidants, spans the previous decades. A new series of complexes of the type [Cu (dien) (2a-2tzn) Y(2)] and [Cu (dienXXY(2)) (2a-5mt)] and of the type [Cu (dptaS) Cl(2)] and [Cu (dptaS) Br(2)] (dptaS = 1, 3-propanediamine) or Schiff mono-base of dipropylenetriamine with 2-thiophene-carboxaldehyde, has been tested for anti-inflammatory and antioxidant activity. The tested compounds inhibit the carrageenin-induced rat paw edema (52.0-82.6%) and present important scavenging activity. Compound 6 is the most potent (82.6%) in the in vivo experiment. Lipophilicity-as R(M) values - has been determined. The results support that in general, adducts of the type [Cu (dienXXY(2)) (2a-5mt)] exhibit increased activity compared to the starting material of type [Cu (dienXXY(2))]. An attempt to correlate the biological results with their structural characteristics and physicochemical parameters has been made.
Assuntos
Aldeídos/química , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Antioxidantes/química , Antioxidantes/farmacologia , Cobre/química , Tiazóis/química , Animais , Carragenina/farmacologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Compostos Heterocíclicos/química , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Ratos , Bases de Schiff/químicaRESUMO
A new series of mixed-ligand mono- or hetero-trihalide Cu(II) complexes of the type [Cu(dienXX)Y(YZ(2))], where dienXX=Schiff dibase of diethylenetriamine with 2-thiophene-carboxaldehyde (dienSS), 2-furaldehyde (dienOO) or 2-pyrrole-2-carboxaldehyde (dienNN), Y=Cl, Br and Z=Br, I was synthesized by the reaction of the precursors of the type [Cu(dienXX)Y]Y with iodine or bromine in 1:1 molar ratio. The distorted square pyramidal configuration of the new homo- and hetero-trihalide Cu(II) mononuclear complexes was identified by C, H, N, Cu analysis, spectroscopic methods (IR, UV-visible), molar conductivity and magnetic measurements. The basal plane consists of three nitrogen atoms of the Schiff base and one halogen (terminal) atom while another axially located trihalogen moiety occupies the fifth side of the square pyramid as a YZ(2) entity, adopting an almost linear configuration. The equilibrium geometry of these complexes was further corroborated by theoretical studies at the B3LYP/DGDZVP level. A series of quantum chemical descriptors (e.g. SOMO (singly occupied molecular orbital) LUMO (lowest occupied molecular orbital), SOMO and LUMO energies, SOMO-LUMO gap, dipole moment, polarizability, molar volume, etc.) have been utilized in order to deduce quantitative structure-activity relationships (QSARs). The effect of the new compounds on the single stranded (ss), double stranded (ds) and pDNA led either to the formation of a DNA-complex cationic adduct, or to its degradation, evidenced by DNA electrophoretic mobility and DNA interaction spectroscopic titration studies. Moreover, the antimicrobial activity of Cu(II) complexes against Gram(+) and Gram(-) bacteria can be attributed to the synergistic action of the dissociation species, namely the cationic [Cu(dienXX)Y](+) and anionic [YZ(2)](-) ones. Finally, de Novo linear regression analysis correlating the bioactivity of these complexes with their structural substituents has been carried out, leading to some interesting qualitative observations/conclusions.
Assuntos
Cobre/química , DNA/metabolismo , Bases de Schiff/química , Brometos/química , Cloretos/química , Cobre/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Modelos Lineares , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Compostos Organometálicos/química , Compostos Organometálicos/metabolismo , Compostos Organometálicos/farmacologia , Relação Quantitativa Estrutura-Atividade , Espectrofotometria Infravermelho , Espectrofotometria UltravioletaRESUMO
A new series of complexes of the type [Cu(dien)(2a-2tzn)Y2] and [Cu(dienXX)(2a-2tzn)Y2] has been tested for anti-inflammatory and antioxidant activity. The tested compounds inhibit significantly the carrageenin induced paw edema (36.4-55.8%) and present important scavenging activities. Although their interaction with the free stable radical DPPH is not high they peroxide anions. Compound 7 is the most potent (55.8%) in the in vivo experiment. Lipophilicity--as RM values and theoretically calculated logP values--has been determined. An attempt to correlate the biological results with their structural characteristics and physicochemical parameters has been done.