RESUMEN
A series of pyrimido[5,4-c]quinoline-2,4-dione derivatives 5a-k were synthesized in moderate yields via a thermolysis reaction of equimolar ratio of 5-arylidine-1,3-dimethylbarbituric acid derivatives 3a-d with aniline derivatives 4a-d at 150-180 °C for 1-2 h. Eight of the synthesized compounds were chosen for a primary in vitro one-dose anticancer assay performed using the full NCI 60 cell panel. Only compound 5b showed moderate GI% at the used dose (10 µM) against four of the tested cell lines corresponding to leukemia SR (GI%: 51), non small-cell lung cancer HOP-92 (GI%: 63), melanoma UACC-62 (GI%: 53) and renal cancer UO-31 (GI%: 69). On the other hand, antimicrobial screening of the whole set of the synthesized compounds was performed against three Gram +ve and two Gram -ve bacterial strains. Results of the antimicrobial screening showed that compounds 5d, 5e, 5f, 5h and 5k have broad-spectrum antibacterial efficacy being moderately active against all the tested Gram +ve and two Gram -ve bacteria. Also, compound 5a showed interesting results being only active against Streptococcus faecalis and both tested Gram -ve strains viz. E. coli and P. aeruginosa. In order to compare the binding mode of the most active compounds 5e and 5f along with the inactive compound 5c we docked these compounds into the empty binding site of topoisomerase II DNA gyrase (PDB ID: 1KZN), and results were compared with the bound inhibitor Clorobiocin.
Asunto(s)
Antibacterianos/farmacología , Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , Antibacterianos/síntesis química , Antiinfecciosos/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Sitios de Unión , Línea Celular Tumoral , Técnicas de Química Sintética , Girasa de ADN/química , Girasa de ADN/metabolismo , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales/métodos , Escherichia coli/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Modelos Moleculares , Simulación del Acoplamiento Molecular , Novobiocina/análogos & derivados , Novobiocina/química , Novobiocina/metabolismo , Novobiocina/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Inhibidores de Topoisomerasa IIRESUMEN
Manganese(II), iron(II), cobalt(II), nickel(II), copper(II), and chromium(III) complexes of (E)-2-(2-(2-hydroxybenzylidene)hydrazinyl)-2-oxo-N-phenylacetamide were synthesized and characterized by elemental and thermal (TG and DTA) analyses, IR, UV-vis and (1)H NMR spectra as well as magnetic moment. Mononuclear complexes are obtained with 1:1 molar ratio except [Mn(HOS)(2)(H(2)O)(2)] and [Co(OS)(2)](H(2)O)(2) complexes which are obtained with 1:2 molar ratios. The IR spectra of ligand and metal complexes reveal various modes of chelation. The ligand behaves as a monobasic bidentate one and coordination occurs via the enolic oxygen atom and azomethine nitrogen atom. The ligand behaves also as a monobasic tridentate one and coordination occurs through the carbonyl oxygen atom, azomethine nitrogen atom and the hydroxyl oxygen. Moreover, the ligand behaves as a dibasic tridentate and coordination occurs via the enolic oxygen, azomethine nitrogen and the hydroxyl oxygen atoms. The electronic spectra and magnetic moment measurements reveal that all complexes possess octahedral geometry except the copper complexes possesses a square planar geometry. From the modeling studies, the bond length, bond angle, HOMO, LUMO and dipole moment had been calculated to confirm the geometry of the ligands and their investigated complexes. The thermal studies showed the type of water molecules involved in metal complexes as well as the thermal decomposition of some metal complexes. The protonation constant of the ligand and the stability constant of metal complexes were determined pH-metrically in 50% (v/v) dioxane-water mixture at 298 K and found to be consistent with Irving-Williams order. Moreover, the minimal inhibitory concentration (MIC) of these compounds against Staphylococcus aureus, Escherechia coli and Candida albicans were determined.
Asunto(s)
Acetanilidas/química , Antiinfecciosos/química , Complejos de Coordinación/química , Hidrazonas/química , Elementos de Transición/química , Acetanilidas/síntesis química , Acetanilidas/farmacología , Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Candida albicans/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/farmacología , Escherichia coli/efectos de los fármacos , Humanos , Hidrazonas/síntesis química , Hidrazonas/farmacología , Ligandos , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Micosis/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Elementos de Transición/síntesis química , Elementos de Transición/farmacologíaRESUMEN
The present work carried out a study on perchlorate mixed-ligand copper(II) complexes which have been synthesized from ethylenediamine derivatives (3a-c) and beta-diketones. These complexes, namely [Cu(DA-Cl)(acac)H(2)O]ClO(4)4, [Cu(DA-Cl)(bzac)H(2)O]H(2)O.ClO(4)5, [Cu(DA-OMe)(acac)H(2)O]ClO(4)6, [Cu(DA-OMe)(bzac)H(2)O]ClO(4)7, [Cu(DA-H)(acac)H(2)O]2H(2)O.ClO(4)8 and [Cu(DA-H)(bzac)H(2)O]ClO(4)9 (where acac, acetylacetonate and bzac, benzoylacetonate) were characterized by elemental analysis, spectral (IR and UV-vis) and magnetic moment measurements. Thermal properties and decomposition kinetics of all complexes are investigated. The interpretation, mathematical analysis and evaluation of kinetic parameters (E, A, DeltaH, DeltaS and DeltaG) of all thermal decomposition stages have been evaluated using Coats-Redfern equation. The biochemical studies showed that, the diamines 3a-c have powerful effects on degradation of DNA and protein. The antibacterial screening demonstrated that, the diamine (DA-Cl), 3b has the maximum and broad activities against Gram +ve and Gram -ve bacterial strains.
Asunto(s)
Cobre/química , Etilenodiaminas/química , Cetonas/química , Percloratos/química , Temperatura , Animales , Antibacterianos/química , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Bovinos , Cobre/farmacología , ADN Bacteriano/metabolismo , Análisis Diferencial Térmico , Electrones , Etilenodiaminas/farmacología , Cetonas/farmacología , Cinética , Ligandos , Magnetismo , Pruebas de Sensibilidad Microbiana , Percloratos/farmacología , Albúmina Sérica Bovina/metabolismo , Espectrofotometría Infrarroja , Superóxidos/metabolismo , TermogravimetríaRESUMEN
Four mixed-ligand copper(II) complexes of the nitrogen ligand bis[N-(p-tolyl)imino]acenaphthene 1 (p-Tol-BIAN). These complexes, namely [Cu(p-Tol-BIAN)2](ClO4)2 2, [Cu(p-Tol-BIAN)(acac)](ClO4) 3, [Cu(p-Tol-BIAN)Cl2] 4 and [Cu(p-Tol-BIAN)(AcOH)(2)](ClO4)2 5, were prepared and characterized. Solvatochromism of the novel copper complexes in various solvents has been studied. Molecular mechanics (MM+) and molecular dynamic simulations have been performed to learn more about the solvatochromic behaviour and the DNA binding affinity of these complexes.
Asunto(s)
Acenaftenos/química , Acenaftenos/farmacología , Cationes Bivalentes/química , Simulación por Computador , Cobre/química , ADN/metabolismo , Solventes/química , Absorción , Animales , Recuento de Células Sanguíneas , Carcinoma de Ehrlich/mortalidad , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Color , Ligandos , Verde de Metilo/química , Ratones , Modelos Moleculares , Conformación Molecular , Electricidad Estática , Tasa de Supervivencia , TermodinámicaRESUMEN
A new series of first-row transition metal complexes with 1-acetylpyridinium chloride-4-benzoyl thiosemicarbazide (H2GPBzIT) have been prepared and characterized by elemental analysis, spectroscopic and magnetic measurements. The proton-ligand ionization constants were determined potentiometrically using Irving-Rossotti technique. The stability constants of complexes were also calculated and were found in agreement with the sequence of stability constants of Irving and Williams. Thermal stability and degradation kinetics have been measured using thermogravimetric analyzer. Kinetic parameters were obtained for each stage of thermal degradation of complexes using Coats-Redfern method.
Asunto(s)
Compuestos Organometálicos/química , Compuestos Organometálicos/síntesis química , Elementos de Transición/química , Betaína/análogos & derivados , Betaína/química , Estabilidad de Medicamentos , Ligandos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Potenciometría , Semicarbacidas/síntesis química , Semicarbacidas/química , Espectrofotometría , Termodinámica , TermogravimetríaRESUMEN
Four mixed-ligand copper(II) complexes containing the rigid bidentate nitrogen ligand bis[N-(p-tolyl)imino]acenaphthene (abb. p-Tol-BIAN) ligand are reported. These complexes, namely [Cu(p-Tol-BIAN)(2)](ClO(4))(2)1, [Cu(p-Tol-BIAN)(acac)](ClO(4)) 2, [Cu(p-Tol-BIAN)Cl(2)] 3 and [Cu(p-Tol-BIAN)(AcOH)(2)](ClO(4))(2)4 (where acac, acetylacetonate and AcOH, acetic acid) have been prepared and characterized by elemental analysis, spectroscopic, magnetic and molar conductance measurements. ESR spectra suggest a square planar geometry for complexes 1 and 2. In complexes 3 and 4, a distorted tetrahedral arrangement around copper(II) centre was suggested. Solvatochromic behavior of all studied complexes indicates strong solvatochromism of their solutions. The observed solvatochromism is mainly due to the solute-solvent interaction between the chelate cation and the solvent molecules. Thermal properties and decomposition kinetics of all complexes are investigated. The kinetic parameters (E, A, Delta H, Delta S and Delta G) of all thermal decomposition stages have been calculated using the Coats-Redfern and other standard equations.
Asunto(s)
Acenaftenos/química , Cobre , Conductividad Eléctrica , Espectroscopía de Resonancia por Spin del Electrón , Ligandos , Modelos Moleculares , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Solventes , Espectrofotometría Infrarroja , TermodinámicaRESUMEN
Two cobalt and two Nickel complexes of bis[N-(2,6-diisopropylphenyl)imino]acenaphthene (Pr-BIAN) ligand, have been synthesized. These complexes, namely [Co(Pr-BIAN)Cl2] 1, [Co(OAc)2 (Pr-BIAN)2](ClO4) 2, [Ni(Pr-BIAN)(NO3)2] 3 and [Ni(Pr-BIAN)2](ClO4)2 4, were characterized by elemental analyses, molar conductance, spectral (IR, UV-Visible and NMR) and magnetic moment measurements. In these complexes the geometries about the metal center are significantly different. While for complexes 2 and 3 an octahedral structure is proposed, in complex 4, square-planar coordination with an almost perfect planar arrangement of two Pr-BIAN ligands around the nickel center is suggested. In 1, two imine nitrogen atoms of Pr-BIAN and two chloride atoms are coordinating in a tetrahedral fashion around the cobalt center. Molecular mechanics (MM+) and semiempirical molecular orbital calculations have been performed for the most biologically active complex 1 and its free ligand Pr-BIAN and compared with inactive ligand bis[N-(p-tolylphenyl)imino]acenaphthene 6, to get insight into their molecular structures and to learn more about their stable molecular conformations.