Di-μ-azido-bis­({N′-[1-(2-pyrid­yl-κN)ethyl­idene]acetohydrazidato-κ2 N′,O}dicopper(II))

The dimeric title compound, [Cu2(C9H10N3O)2(N3)2], is located on a crystallographic inversion center. The Cu atom is coordinated by a tridentate anionic hydrazone ligand and two bridging azide ligands in a distorted square-pyramidal coordination geometry. The non-bonding Cu⋯Cu distance is 3.238 (1) Å. Non-classical inter­molecular C—H⋯N hydrogen bonds link the dimers into chains along the c axis

Dichlorido{N′-[1-(2-pyridin-2-yl)ethyl­idene]acetohydrazide-κ2 N′,O}copper(II)

In the title compound, [CuCl2(C9H11N3O)], the CuII atom is in a distorted square-pyramidal CuCl2N2O coordination geometry. The tridentate acetohydrazide ligand chelates in a meridional fashion. The chloride ligand in the axial position forms a long Cu—Cl distance of 2.4892 (9) Å. In contrast, the Cu—Cl distance from the equatorial chloride ligand is much shorter [2.2110 (7) Å]. Inter­molecular N—H⋯Cl and C—H⋯Cl hydrogen bonds link the complexes into a three-dimensional network

Estudo do perfil farmacológico de novos complexos metálicos de hidrazonas derivadas de piridina e imidazóis

Exportado OPUSMade available in DSpace on 2019-08-09T16:25:19Z (GMT). No. of bitstreams: 1 tese_angel_amado_recio_despaigne.pdf: 15858855 bytes, checksum: 1603b2240b81dcab3826bafcfa54adee (MD5) Previous issue date: 3No presente trabalho foi feita a síntese e a caracterização estrutural de hidrazonas derivadas de piridina e de imidazol. Foram também obtidos complexos das hidrazonas derivadas de piridina com zinco(II), cobre(II) e estanho(IV). O perfil farmacológico das hidrazonas e seus complexos metálicos foi investigado. Foram obtidas doze hidrazonas derivadas de imidazol e as estruturas cristalinas de quatro compostos foram determinadas. Foi avaliada a atividade antibacteriana dos derivados de imidazol frente a bactérias Pseudomonas aeruginosa, Enterococcus faecalis e Staphylococcus aureus, mas os compostos não apresentaram atividade apreciável. Foi também avaliada a atividade antifúngica, dos compostos frente aos fungos filamentosos, Cladosporium cladosporioides, Aspergillus flavus e contra leveduras Candida albicans e Candida glabrata. 4(5)imidazol-carboxaldeído-benzoilhidrazona [4(5)ImPh], 4(5)imidazol-carboxaldeído-paranitro-benzoilhidrazona [4(5)ImpNO2Ph] e 4-(imidazol-1-il)acetofenona-para-nitrobenzoilhidrazona [4ImAcpNO2Ph] foram muito ativos frente a C. glabrata, com valores de concentração inibitória de 50% do crescimento (CIM50) menores que os da nistatina, fármaco de controle. 4(5)imidazol-carboxaldeído-para-cloro-benzoilhidrazona [4(5)ImpClPh] e [4(5)ImpNO2Ph] mostraram alta atividade frente a C. cladosporioides. Os resultados sugerem que a presença de substituintes retiradores de elétrons na posição para do anel fenila favorece a atividade nos compostos estudados. Foram obtidas dez hidrazonas derivadas de piridina, sendo duas de 2-formilpiridina, quatro de 2-acetilpiridina e quatro de 2-benzoilpiridina. As estruturas cristalinas de cinco desses compostos foram determinadas. As hidrazonas apresentaram equilíbrio isomérico Z e E em solução, onde o isômero E está em maior proporção nos derivados de 2-formilpiridina e 2-acetilpiridina, e o isômero Z é o majoritário para as hidrazonas derivadas de 2-benzoilpiridina. Esses compostos apresentaram uma atividade antifúngica significativa frente a todos os microorganismos testados, com valores de CIM da mesma ordem ou inferior aos dos fármacos de controle (nistatina e fluconazol). Além disso, essas hidrazonas apresentaram atividade citotóxica contra células de gliobastoma U87 (que expressam a proteína pro-apoptótica p53) e T98 (que expressam a proteína p53 mutante) com valores de IC50 na ordem de nanomolar, com bons índices terapêuticos. Cinco compostos mostraram-se mais ativos que o fármaco de controle (etoposídeo). Estudos SAR sugerem que propriedades estéreo-eletrônicas influenciam a atividade citotóxica das hidrazonas contra as células estudadas. Em geral, as hidrazonas derivadas de 2-acetipiridina mostraram melhor perfil farmacológico por serem mais ativas tanto frente aos microorganismos como frente às células tumorais. Foram obtidos complexos de zinco(II) e cobre(II) das hidrazonas derivadas de piridina. Os complexos de zinco(II) são do tipo [Zn(HL)Cl2], onde o ligante neutro encontra-se coordenado ao metal de forma tridentada na configuração E. Seis compostos tiveram suas estruturas cristalinas determinadas. Neste caso a coordenação não fez melhorar a atividade antimicrobiana dos ligantes. Os compostos de cobre(II) apresentaram dois tipos de estruturas, [Cu(HL)Cl2] e [Cu(L)Cl]. Nos primeiros, a hidrazona neutra se liga ao metal de forma tridentada juntamente com dois íons cloreto e nos últimos a hidrazona coordena-se sob a forma aniônica juntamente com um íon cloreto. De modo geral, observou-se uma melhoria da atividade antimicrobiana pela coordenação ao cobre(II). Os melhores resultados foram obtidos para os complexos [Cu(L)Cl] em que HL = 2-acetilpiridina-para-clorofenilhidrazona e HL = 2-benzoilpiridina-paraclorofenilhidrazona frente a C. albicans os quais apresentaram valores de CIM menores que o fluconazol. Os complexos de cobre(II) apresentaram atividade citotóxica superior às das hidrazonas livres frente às células de glioblastoma U87. Estudos de interação com DNA mostraram duas formas diferentes de interação. Três compostos apresentaram um perfil típico de intercalação enquanto seis compostos interagem provavelmente por outro mecanismo. Foram obtidos doze complexos de estanho(IV) das hidrazonas derivadas de piridina, de formula geral [RSn(HL)Cl2] em que R = n-butil ou R = fenil. Em todos os casos, uma molécula de hidrazona aniônica se liga ao átomo central de modo tridentado, juntamente a um grupo felina ou butila, e dois íons cloreto. As estruturas cristalinas de sete desses compostos foram determinadas. Os complexos organoestânicos apresentaram maior atividade antifúngica que os ligantes livres frente a A. flavus, C. glabrata e C. albicans, com menores valores de CIM que a nistatina e o fluconazol. Os complexos de estanho(IV) apresentaram fluorescência, com valores de rendimento quântico na ordem do sulfato de quinina em meio aquoso. Além disso, um aumento da intensidade de fluorescência foi observado com a adição de um surfactante micelar na solução. Esse resultado é interessante porque possibilitaria uma posterior aplicação desses compostos como marcadores fluorescentes.In the present work, new pyridine and their copper(II), zinc(II), and tin(IV) complexes were obtained and characterized, imidazole-derived hydrazones were also estudied. Crystal structures of different compounds were determined. The pharmacological profile of allcompounds was investigated. Twelve imidazole-derived hydrazones were obtained. Four crystal structures were determinated. The antibacterial activity of the hydrazones was evaluated against Pseudomonasaeruginosa, Enterococcus faecalis and Staphylococcus aureus, but the compounds showed no appreciable activity. The antifungical activity of the compounds was evaluated against filamentous fungi Cladosporium cladosporioides and Aspergillus flavus and against Candidaalbicans and C. glabrata yeasts. 4(5)-imidazole-carboxaldehyde-benzoylhydrazone [4(5)ImPh],4(5)-imidazole-carboxaldehyde-para-nitro-benzoylhydrazone [4(5)ImpNO2Ph] and 4- (imidazole-1-yl)acetophenone-para-nitro-benzoylhydrazone [4ImAcpNO2Ph] showed lower MIC50 values than the reference drug nistatin, whereas compounds 4(5)ImpClPh and 4(5)ImpNO2Ph proved to be very active against C. cladosporioides. In this case, a possiblerelationship between the presence of electron withdrawing para-substituents and the increasing in antifungal activity was observed.Ten pyridine-derived hydrazones were obtained from 2-formylpyridine, 2acetylpyridine and 2benzoylpyridine. The crystal structures of six compounds were determined. These compounds exist as E and Z isomers in solution. The E isomer is the major form in 2-formylpyridine- and 2acetylpyridine-derived hydrazones, while the Z isomer predominates for 2-benzoylpyridine derivatives.The pharmacological profiles of these compounds were very interesting since they showed significant antifungal activity with MIC values lower or in the same order of magnitude as the reference drugs fluconazole and nistatin. In addition, the studied hydrazones showed highcitotoxic activity against U87 (expressing wild-type p53 protein) and T98 (expressing mutant p53 protein) glioma cells. Five hydrazones showed IC50 values in nanomolar concentrations with good therapeutic indexes. SAR studies suggested that stereo-electronic properties are importantfor citotoxic activity. In general, the 2-acetylpyridine-derived hydrazones showed better phamacological profile than the 2-formylpyridine- and 2-benzoylpyridine-derived analogues. Copper(II) and zinc(II) complexes were obtained with the pyridine-derived hydrazones.The zinc(II) complexes presented the general formula [Zn(HL)Cl2] whith a neutral hydrazone attached in a tridentate form to the metal ion in the E configuration. The crystal structures of six complexes were determined. Unfortunately, these complexes were inactive against fungi andbacteria. Copper(II) complexes were obtained with general formula [Cu(HL)Cl2] or [Cu(L)Cl]. In the first case, a neutral hydrazone is coordinated to the metal center as a tridentate chelatingligand, together with two chloride ions, while, in the second an anionic hydrazone is attached to the metal center along with one chloride ion. In all cases the hydrazone adopts the E configuration.The copper(II) complexes demonstrated an important pharmacological profile. Upon coordination, significant increase of the antimicrobial activity was observed. In fact, complexes [Cu(2AcpClPh)Cl] and [Cu(2BzpClPh)Cl], with 2-acetylpyridine-para-chlorophenylhydrazoneand 2-benzoylpyridine para-chlorophenylhydrazone, respectively showed lower values of MIC than fluconazole against C. albicans fungi. Some of these complexes also showed high cytotoxicity against U87 glioma cells, with a higher cytotoxic effect than the free hydrazones. Studies of the interaction of the complexes with DNA revealed that some of the complexes showed a typical intercalation profile while others probably present a different way of interaction. Tin(IV) complexes with the general formula [RSn(HL)Cl2] R = n-butyl or R = phenyl were prepared with the pyridine-derived hydrazones. In all complexes an anionic hydrazone iscoordinated to metal center as a tridentate ligand together with a phenyl or a n-butyl group and two chloride ions. The crystal structures of seven organotin complexes were determined. The complexes showed higher antifungal activity than their respective ligands against A. flavus, C.glabrata e C. albicans. The tin(IV) complexes were fluorescent with quantum yield values similar to quinine sulfate. An increase in the intensity of fluorescence was observed with the addition of smallamounts of micelar surfactant tween. This property could make these complexes useful as fluorescent probes

ROS-Mediated Cytotoxic Effect of Copper(II) Hydrazone Complexes against Human Glioma Cells

2-Acetylpyridine acetylhydrazone (H2AcMe), 2-benzoylpyridine acetylhydrazone (H2BzMe) and complexes [Cu(H2AcMe)Cl2] (1) and [Cu(H2BzMe)Cl2] (2) were assayed for their cytotoxicity against wild type p53 U87 and mutant p53 T98 glioma cells, and against MRC-5 fibroblast cells. Compounds 1 and 2 proved to be more active than the corresponding hydrazones against U87, but not against T98 cells. Compound 1 induced higher levels of ROS than H2AcMe in both glioma cell lines. H2AcMe and 1 induced lower levels of ROS in MRC5 than in U87 cells. Compound 2 induced lower levels of ROS in MRC5 than in T98 cells. The cytotoxic effect of 1 in U87 cells could be related to its ability to provoke the release of ROS, suggesting that the cytotoxicity of 1 might be somehow p53 dependent

Complexation of 2-acetylpyridine- and 2-benzoylpyridine-derived hydrazones to copper(II) as an effective strategy for antimicrobial activity improvement

Complexes [Cu(2AcPh)Cl]center dot 2H(2)O (1), [Cu(2AcpClPh)Cl]center dot 2H(2)O (2), [Cu(2AcpNO(2)Ph)Cl] (3), [Cu(2BzPh)Cl] (4). [Cu(2BzpClPh)Cl] (5) and [Cu(2BzpNO(2)Ph)Cl] (6) were obtained with 2-acetylpyridine-phenylhydrazone (H2AcPh), 2-acetylpyridine-para-chloro-phenylhydrazone (H2AcpClPh), 2-acetylpyridine-para-nitro-phenylhydrazone (H2AcpNO(2)Ph), 2-benzoylpyridine-phenylhydrazone (H2BzPh), 2-benzoylpyridine-para-chloro-phenylhydrazone (H2BzpClPh) and 2-benzoylpyridine-para-nitro-phenylhydrazone (H2BzpNO(2)Ph). The hydrazones showed poor antibacterial effect against Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa but demonstrated significant antifungal activity against Candida albicans. Upon coordination to copper(II) the antibacterial and antifungal activities appreciably increased. H2AcpClPh, H2BzpClPh and their copper(II) complexes (2) and (5), respectively, were as active as fluconazole against C. albicans. (C) 2012 Elsevier Ltd. All rights reserved.CNPqCNPqINCT-INOFAR [Proc. CNPq 573.364/2008-6]INCTINOFARFAPESP (Brazil)FAPESP (Brazil)CONICET (Argentina)CONICET (Argentina

Copper(II) and zinc(II) complexes with 2-benzoylpyridine-methyl hydrazone

2-Benzoylpyridine-methyl hydrazone (HBzMe) has been obtained as well as its copper(II) [Cu(HBzMe)Cl(2)] (1) and zinc(II) [Zn(HBzMe)Cl(2)] (2) complexes. Upon re-crystallization in 1 - 9 DMSO:acetone conversion of I into dimeric [Cu(BzMe)Cl](2) (1a) occurred. The crystal structures of HBzMe, 1, 1a, and 2 were determined. HBzMe adopts the ZE conformation in the solid. In all complexes the hydrazone adopts the E configuration to attach to the metal through the N(py)-N2-O chelating system. In 1 and 2 a neutral hydrazone coordinates to the metal center while in 1a deprotonation occurs with coordination of an anionic ligand. la presents a dimeric structure. having two copper(II) ions per asymmetric unit. Two chlorides are also present in the copper coordination sphere, which act as bridging ligands and connect the copper centers to each other. (C) 2008 Elsevier B.V. All rights reserved.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)CapesCNPqConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP (Brazil)Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina (CONICET)CONICET (Argentina

Structural studies on zinc(II) complexes with 2-benzoylpyridine-derived hydrazones

2-Benzoylpyridine-phenylhydrazone (H2BzPh), 2-benzoylpyridine-para-chloro-phenylhydrazone (H2BzpClPh), and 2-benzoylpyridine-para-nitro-phenyl (H2BzpNO(2)Ph) hydrazone were obtained and fully characterized, as well as their zinc(II) complexes [Zn(H2BzPh)Cl(2)] (1), [Zn(H2BzClPh)Cl(2)] (2) and [Zn(H2BzpNO(2)Ph)Cl(2)] (3). During the syntheses of complex 1 a second product crystallized, which was characterized as [Zn(2BzPh)(2)] (1a). Upon re-crystallization in 1: 9 DMSO: acetone conversion of 2 into [Zn(H2BzpClPh)Cl2] center dot H(2)O (2a) and of 3 into [Zn(2BzpNO(2)Ph)Cl(DMSO)] (3a) occurred. The crystal structures of 1a, 2a and 3a were determined. In 1a the two nearly perpendicular H2BzPh ligands give rise to a distorted octahedral environment around the metal. The 5-fold coordination around the metal is completed with two chloride ions in 2a and with one chloride and one oxygen atom from DMSO in 3a. (c) 2008 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Capes and CNPq (Brazil)CONICET (Argentina)Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina (CONICET

Structural Studies and Investigation on the Activity of Imidazole-Derived Thiosemicarbazones and Hydrazones against Crop-Related Fungi

New imidazole derived thiosemicarbazones and hydrazones were prepared by condensation of 4(5)-imidazole carboxaldehyde, 4-(1H-imidazole-1-yl)benzaldehyde and 4-(1H-imidazole-1-yl)acetophenone with a thiosemicarbazide or hydrazide. All compounds were characterized by quantitative elemental analysis, IR and NMR techniques. Eight structures were determined by single crystal X-ray diffraction. The antifungal activities of the compounds were evaluated. None of the compounds exhibited significant activity against Aspergillus flavus and Candida albicans, while 4(5)-imidazolecarboxaldehyde thiosemicarbazone (ImT) and 4-(1H-imidazole-1-yl)benzaldehyde thiosemicabazone (4ImBzT) were highly and selectively active against Cladosporium cladosporioides. 4(5)-Imidazolecarboxaldehyde benzoyl hydrazone (4(5)ImPh), 4(5)-imidazolecarboxaldehyde-para-chlorobenzoyl hydrazone (4(5)ImpClPh), 4(5)-imidazolecarboxaldehyde-para-nitrobenzoyl hydrazone (4(5)ImpNO2Ph), 4-(imidazole-1-yl)acetophenone-para-chloro-benzoyl hydrazone (4ImAcpClPh) and 4-(imidazole-1-yl)acetophenone-para-nitro-benzoylhydrazone (4ImAcpNO2Ph) were highly active against Candida glabrata. 4(5)ImpClPh and 4(5)ImpNO2Ph were very effective against C. cladosporioides. In many cases, activity was superior to that of the reference compound nystatin