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1.
Dalton Trans ; 48(33): 12496-12511, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31361288

RESUMO

Three tetranuclear (1-3) complexes and a mononuclear (4) palladium(ii) complex were synthesized from 3-acetyl-chromen-2-one Schiff base ligands [H2-3MAC-Rtsc] (where R = H [H2-3MAC-tsc]; CH3[H2-3MAC-mtsc]; C2H5[H2-3MAC-etsc] or C6H5[H2-3MAC-ptsc]) and potassium tetrachloropalladate. Their formation was confirmed by spectroscopic techniques and X-ray crystallographic analysis. Their ability to bind with DNA and albumin was analysed by using absorption and emission titrations. The MTT assay was carried out to analyze the anticancer potential of the ligands and synthesized complexes against HepG2 (human liver cancer) and HT-29 (human colon cancer) cells. In addition, the compounds were less toxic when tested against the human normal keratinocyte cells (HaCaT). Ligands and complexes displayed better cytotoxicity with lower IC50 values than the standard drug cisplatin. Further AO-EB and DAPI staining assays were carried out to detect the mode of cell death induced by the complexes i.e. apoptosis or necrosis. The complex 3 showed better cytotoxicity and was further subjected to flow cytometric analysis. The results suggested that the complex 3 induced apoptotic cell death.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cromonas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Cromonas/química , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HT29 , Células Hep G2 , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Ligantes , Modelos Moleculares , Estrutura Molecular , Imagem Óptica , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/farmacologia , Relação Estrutura-Atividade
2.
Eur J Med Chem ; 168: 123-133, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30818174

RESUMO

The 1:1 stoichiometric reactions of 3-methoxy salicylaldehyde-4(N)-substituted thiosemicarbazones (H2L1-4) with [RuCpCl(PPh3)2] was carried out in methanol. The obtained complexes (1-4) were characterized by analytical, IR, absorption and 1H NMR spectroscopic studies. The structures of ligand [H2-3MSal-etsc] (H2L3) and complex [RuCp(Msal-etsc) (PPh3)] (3), were characterized by single crystal X-ray diffraction studies. The interaction of the ruthenium(II) complexes (1-4) with calfthymus DNA (CT-DNA) has been explored by absorption and emission titration methods. Based on the observations, an intercalative binding mode of DNA has been proposed. The protein binding abilities of the new complexes were monitored by quenching the tryptophan and tyrosine residues of BSA, as model protein. From the studies, it was found that the new ruthenium metallacycles exhibited better affinity than their precursors. The free radical scavenging assay suggests that all complexes effectively scavenged the DPPH radicals as compared to that of standard control ascorbic acid and scavenging activities of complexes are in the order of 4 > 2 > 3 > 1. In addition, ruthenium(II) complexes (2-4) also exhibited an excellent in vivo antioxidant activity as it was able to increase the survival of worms exposed to lethal oxidative and thermal stresses possibly through reducing the intracellular ROS levels. It was interesting to note that complexes 2-4 failed to increase the lifespan of mev-1 mutant worms having shortened lifespan due to the over production of free radicals. This data confirmed that complexes 2-4 conferred stress resistance in C. elegans, but they also require an endogenous detoxification mechanism for doing so. The genetic and reporter gene expression analysis revealed that complexes 2-4 maintained the intracellular redox status and offered stress protection through transactivation of antioxidant defence machinery genes gst-4 and sod-3 which are directly regulated by SKN-1 and DAF-16 transcription factors, respectively. Altogether, our results suggested that complexes 2-4 might play a crucial role in stress modulation and they perhaps exert almost similar effects in higher models, which is an important issue to be validated in future.


Assuntos
Antioxidantes/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Rutênio/farmacologia , Animais , Antioxidantes/síntese química , Antioxidantes/química , Caenorhabditis elegans/metabolismo , Relação Dose-Resposta a Droga , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Rutênio/química , Relação Estrutura-Atividade
3.
Sci Rep ; 8(1): 7688, 2018 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-29769649

RESUMO

New ruthenium(II) complexes were synthesised and characterized by various spectro analytical techniques. The structure of the complexes 3 and 4 has been confirmed by X-ray crystallography. The complexes were subjected to study their anti-oxidant profile and were exhibited significantly greater in vitro DPPH radical scavenging activity than vitamin C. We found that complexes 1-4 confered tolerance to oxidative stress and extend the mean lifespan of mev-1 mutant worms and wild-type Caenorhabditis elegans. Further, mechanistic study and reporter gene expression analysis revealed that Ru(ƞ6-p-cymene) complexes maintained the intracellular redox status and offers stress resistance through activating JNK-1/DAF-16 signaling axis and possibly by other antioxidant response pathway. Notably, complex 3 and 4 ameliorates the polyQ (a Huntington's disease associated protein) mediated proteotoxicity and related behavioural deficits in Huntington's disease models of C. elegans. From these observations, we hope that new Ru(ƞ6-p-cymene) complexes could be further considered as a potential drug to retard aging and age-related neurodegenerative diseases.


Assuntos
Antioxidantes/farmacologia , Proteínas de Caenorhabditis elegans/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Compostos Organometálicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Rutênio/química , Animais , Antioxidantes/química , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/genética , Cristalografia por Raios X , Fatores de Transcrição Forkhead/química , Fatores de Transcrição Forkhead/genética , Longevidade , Proteínas Quinases Ativadas por Mitógeno/química , Proteínas Quinases Ativadas por Mitógeno/genética , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Compostos Organometálicos/química , Peptídeos/administração & dosagem , Conformação Proteica , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
4.
Spectrochim Acta A Mol Biomol Spectrosc ; 200: 246-262, 2018 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-29694929

RESUMO

A series of 3-acetyl-8-methoxycoumarin appended thiosemicarbazones (1-4) was prepared from the reaction of 3-acetyl-8-methoxycoumarin with 4(N)-substituted thiosemicarbazides in a view of ascertaining their biological properties with the change of N-terminal substitution in the thiosemicarbazide moiety. Comprehensive characterization was brought about by various spectral and analytical methods. The molecular structures of all the compounds were determined by single crystal X-ray diffraction analysis. Binding studies with Calf thymus DNA (CT-DNA) and proteins such as Bovine Serum Albumin (BSA) and Human Serum Albumin (HSA) indicated an intercalative mode of binding with DNA and static quenching mechanism with proteins. The compounds cleaved plasmid DNA (pBR322) and acted well as free radical scavengers. A good spectrum of antimicrobial activity was observed against four bacterial and five fungal pathogens. The compounds exhibited profound antiproliferative activity on MCF-7 (human breast cancer) and A549 (human lung carcinoma) cell lines. Assay on human normal keratinocyte cell line HaCaT showed that the compounds were non-toxic to normal cells.


Assuntos
Antineoplásicos/farmacologia , Cumarínicos/farmacologia , Bases de Schiff/farmacologia , Células A549 , Animais , Anti-Infecciosos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antioxidantes/farmacologia , Bovinos , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Cumarínicos/síntese química , Cumarínicos/química , Cristalografia por Raios X , DNA/metabolismo , Etídio/química , Humanos , Ligação de Hidrogênio , Concentração Inibidora 50 , Cinética , L-Lactato Desidrogenase/metabolismo , Células MCF-7 , Conformação Molecular , Nitritos/metabolismo , Bases de Schiff/síntese química , Bases de Schiff/química , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Temperatura , Viscosidade
5.
J Photochem Photobiol B ; 180: 77-88, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29413705

RESUMO

New Schiff base ligands are prepared by the condensation of 7-hydroxy-3-formylchromone with semicarbazone and phenyl semicarbazone. The complexation of these ligands with Cu(II) ion is proposed in the light of spectral studies (IR, UV-Vis, 1H NMR, 13C NMR, Mass and ESR). In the complexes 1 and 2, the ligands coordinate to the Cu(II) ion in a neutral fashion via ONO donor atoms. The single crystal XRD studies reveal a slightly distorted square-pyramidal geometry for cationic complex (1) and an octahedral geometry for neutral complex (2). Preliminary biological studies such as DNA and Protein binding are carried out by using absorption and emission titration methods. Observation of intercalative mode of binding with Calf Thymus DNA (CT-DNA) is confirmed by means of viscosity measurements. The micro-environmental changes occurring in Bovine Serum Albumin (BSA) and Human Serum Albumin (HSA) are monitored via three dimensional (3D) fluorescence studies. The compounds ability in inhibiting microbial growth is tested against different pathogens. MCF-7 (human breast cancer) and A549 (human lung carcinoma) cell lines are utilized to check the anticancer potential of the synthesized compounds by using MTT, LDH and NO assays. The results show that complexes 1 and 2 exhibited potent cytotoxic activity over standard drug cisplatin.


Assuntos
Anti-Infecciosos/síntese química , Cromonas/química , Complexos de Coordenação/química , Cobre/química , Células A549 , Animais , Anti-Infecciosos/farmacologia , Cátions/química , Bovinos , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/metabolismo , Complexos de Coordenação/toxicidade , DNA/química , DNA/metabolismo , Fungos/efeitos dos fármacos , Humanos , Células MCF-7 , Conformação Molecular , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Ligação Proteica , Pseudomonas aeruginosa/efeitos dos fármacos , Bases de Schiff/química , Semicarbazonas/química , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo
6.
Indian J Surg ; 79(4): 357-359, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28827913

RESUMO

Organo-axial gastric volvulus is a rare postoperative complication of stomach surgeries. A case is presented in which a 43-year-old patient developed acute gastric volvulus 14 months after a laparoscopic fundoplication, diagnosed by preoperative CT scan, and treated by reduction of the volvulus, closing the gap in the pars flaccida, and a sham gastro-jejunostomy, all done laparoscopically. This is being published to highlight one of the rare complications of gastric surgery, which can be treated successfully with the laparoscope.

7.
J Photochem Photobiol B ; 167: 45-57, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28039789

RESUMO

A series of new water soluble nickel(II) complexes containing triphenylphosphine and 4-methoxysalicylaldehyde-4(N)-substituted thiosemicarbazones were synthesized and characterized. Crystallographic investigations confirmed the structure of the complexes (1-4) having the general structure [Ni(4-Msal-Rtsc)(PPh3)] (Where R=H (1); CH3 (2); C2H5 (3); C6H5 (4)) which showed that thiosemicarbazone ligands coordinated to nickel(II) ion as ONS tridentate bibasic donor. DNA/BSA protein binding ability of the ligands and their new complexes were studied by taking calf-thymus DNA (CT-DNA) and Bovine serum albumin (BSA) through absorption and emission titrations. Ethidium bromide (EB) displacement study showed the intercalative binding trend of the complexes to DNA. From the albumin binding studies, the mechanism of quenching was found as static and the alterations in the secondary structure of BSA by the compounds were confirmed with synchronous spectral studies. The binding affinity of the complexes to CT-DNA and BSA has the order of [Ni(4-Msal-etsc)(PPh3)] (3) >[Ni(4-Msal-mtsc)(PPh3)] (2) >[Ni(4-Msal-tsc)(PPh3)] (1) >[Ni(4-Msal-ptsc)(PPh3)] (4). In vitro cytotoxicity of the complexes was tested on human lung cancer cells (A549), human cervical cancer cells (HeLa), human liver carcinoma cells (Hep G2). All the complexes exhibited significant activity against three cancer cells. Among them, complex 4 exhibited almost 2.5 fold activity than cisplatin in A549 and HepG2 cell lines. In HeLa cell line, the complexes exhibited significant activity which is less than cisplatin. While comparing the activity of the complexes in A549 and HepG2 cell lines it falls in the order 4>1>2>3>cisplatin. The results obtained from DNA, protein binding and cytotoxicity studies, it is concluded that the cytotoxicity of the complexes as determined by MTT assay were not unduly influenced by the complexes having different binding efficiency with DNA and protein. The complexes exhibited good spectrum of antibacterial activity against four pathogenic bacteria such as E. faecalis (gram +ve), S. aureus (gram +ve), E. coli (gram -ve) and P. aeruginosa (gram -ve).


Assuntos
Antibacterianos/farmacologia , DNA/metabolismo , Níquel/farmacologia , Soroalbumina Bovina/metabolismo , Água/química , Animais , Antibacterianos/química , Bovinos , Linhagem Celular Tumoral , Cristalografia por Raios X , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Níquel/química , Ligação Proteica , Solubilidade , Análise Espectral
8.
Eur J Med Chem ; 82: 584-99, 2014 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-24946146

RESUMO

A series of novel nickel(II) thiosemicarbazone complexes(1-4) have been prepared and characterized by various spectral, analytical techniques and X-ray crystallography. Further, their efficacy to interact with CT-DNA/BSA has been explored. From the binding studies, it is inferred that complex 4 found to be more active than other complexes. The complexes bound with CT-DNA by intercalation mode. Moreover, static quenching was observed for their interaction with BSA. The new complexes were tested for their in vitro cytotoxicity against human lung adenocarcinoma (A549) cell line. The results showed that the new complexes exhibited significant degree of cytotoxicity at given experimental condition. Further, the results of LDH and NO release supported the cytotoxic nature of the complexes. The observed cytotoxicity of the complexes may be routed through ROS-hypergeneration and lipid-peroxidation with subsequent depletion of cellular antioxidant pool (GSH, SOD, CAT, GPx and GST) resulted in the reduction of mitochondrial-membrane potential, caspase-3 activation and DNA fragmentation. Thus, the data from the present study disclose that the complexes could induce apoptosis in A549 cells through mitochondrial mediated fashion and inhibited the migration of lung cancer cells and by metastasis.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , DNA/efeitos dos fármacos , Níquel/química , Compostos Organometálicos/farmacologia , Soroalbumina Bovina/efeitos dos fármacos , Tiossemicarbazonas/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antioxidantes/metabolismo , Bovinos , Proliferação de Células/efeitos dos fármacos , DNA/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Mitocôndrias/metabolismo , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
9.
Bioorg Med Chem ; 21(21): 6742-52, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23993327

RESUMO

A series of four new thiosemicarbazone complexes of palladium have been synthesized, characterized and evaluated for their DNA/protein binding with CT-DNA and BSA, respectively. The new complexes bound to CT-DNA by intercalation mode and in protein binding studies, the complexes bound to BSA binding mechanism was found as static quenching. Among them the complex 4 had a strong binding affinity with BSA. In addition, in vitro cytotoxic studies were carried out on lung cancer (A549) and liver cancer (HepG2) cell lines and found that the complexes exhibited better activity than their parent thiosemicarbazone analogues. The complex 3 exhibited better activity than other complexes and this fact supported by the increased accumulation of the complexes in to the cancer cells which are evident from inter cellular uptake studies.


Assuntos
Complexos de Coordenação/síntese química , DNA/metabolismo , Paládio/química , Soroalbumina Bovina/metabolismo , Tiossemicarbazonas/química , Animais , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/metabolismo , Complexos de Coordenação/toxicidade , Cristalografia por Raios X , DNA/química , Células Hep G2 , Humanos , Cinética , Conformação Molecular , Nitritos/metabolismo , Ligação Proteica , Soroalbumina Bovina/química
10.
J Biol Inorg Chem ; 18(2): 233-47, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23274397

RESUMO

Three new nickel(II) thiosemicarbazone complexes have been synthesized and characterized by analytical, spectral, and single-crystal X-ray diffraction studies. In complex 1, the ligand 2-hydroxy-1-naphthaldehydethiosemicarbazone coordinated as a monobasic tridentate donor, whereas in complexes 2 and 3, the ligands salicylaldehyde-4(N)-ethylthiosemicarbazone and 2-hydroxy-1-naphthaldehyde-4(N)-ethylthiosemicarbazone coordinated as a dibasic tridentate donor. The DNA binding ability of the complexes in calf thymus DNA was explored by absorption and emission titration experiments. The antioxidant property of the new complexes was evaluated to test their free-radical scavenging ability. In vitro cytotoxicity assays were performed for the new complexes in A549 and HepG2 cell lines. The new compounds overcome cisplatin resistance in the A549 cell line and they were also active in the HepG2 cell line. The cellular uptake study showed the accumulation of the complexes in tumor cells depended on the nature of the ligand attached to the nickel ion.


Assuntos
Antineoplásicos/química , Complexos de Coordenação/química , DNA/química , Níquel/química , Tiossemicarbazonas/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Compostos de Bifenilo/química , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/metabolismo , Complexos de Coordenação/farmacologia , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Eletroquímica , Formazans/química , Formazans/metabolismo , Depuradores de Radicais Livres/química , Radicais Livres/química , Células Hep G2 , Humanos , Ligação de Hidrogênio , Concentração Inibidora 50 , L-Lactato Desidrogenase/metabolismo , Modelos Moleculares , Conformação Molecular , Óxido Nítrico/metabolismo , Oxirredução , Picratos/química , Espectrofotometria Infravermelho , Sais de Tetrazólio/química , Sais de Tetrazólio/metabolismo , Tiossemicarbazonas/metabolismo , Tiossemicarbazonas/farmacologia
11.
Dalton Trans ; 41(31): 9323-36, 2012 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-22729216

RESUMO

One pot synthesis of three structurally different Ni(II) thiosemicarbazone complexes 1, 2 and 3 were obtained from the reaction between [NiCl(2)(PPh(3))(2)], 1,2-bis(diphenylphosphino)ethane, and [H(2)-(Sal-tsc)]. The obtained products were characterized by various spectral and analytical techniques. From the X-ray crystallographic analysis, an unexpected N-arylation on the coordinated salicylaldehydethiosemicarbazone was found in complex 2. The comparative biological evolutions such as DNA/protein binding, antioxidant, cytotoxicity (MTT, LDH, and NO) and cellular uptake studies have been examined for [Ni(Sal-tsc)(PPh(3))] (1) and [(Ni(Sal-tsc))(2)(µ-dppe)] (3). When comparing the cytotoxicity of the complexes, 1 exhibited higher activity than 2 and 3 and by comparing with standard cis-platin, both of them were found to exhibit better activity under identical conditions.


Assuntos
Níquel/química , Tiossemicarbazonas/química , Compostos de Bifenilo/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , DNA/metabolismo , Radicais Livres/química , Humanos , L-Lactato Desidrogenase/metabolismo , Ligantes , Muramidase/metabolismo , Níquel/farmacologia , Óxido Nítrico/metabolismo , Picratos/química , Tiossemicarbazonas/farmacologia
12.
J Young Pharm ; 4(1): 3-12, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22523453

RESUMO

The present investigation reports the design and evaluation of six-hour extended release film-coated matrix tablets of cephalexin using different grades of hydrophilic polymer hydroxypropylmethylcellulose (HPMC) employing direct compression method. The preformulation studies performed included the physical compatibility studies, Differential Scanning Calorimetry analysis, drug characterization using Fourier Transform Infra Red spectroscopic analysis and particle size analysis using sieve method. The tablets were evaluated for weight variation, hardness, thickness and friability. Results of the studies indicate that the polymers used have significant release-retarding effect on the formulation. The dissolution profile comparison of the prepared batches P1 to P8 and market preparation (Sporidex AF 375) was done by using Food and Drug Administration-recommended similarity factor (f(2)) determination. The formulation P8 (10% HPMC K4M, 15% HPMC 15cps) with a similarity factor (f(2)) of 77.75 was selected as the optimized formulae for scale-up batches. The dissolution data of the best formulation P8 was fitted into zero order, first order, Higuchi and Korsemeyer-Peppas models to identify the pharmacokinetics and mechanism of drug release. The results of the accelerated stability study of best formulation P8 for three months revealed that storage conditions were not found to have made any significant changes in final formulation F3. The release of cephalexin was prolonged for 6 h by using polymer combinations of HPMC and a twice daily matrix tablet was formulated.

13.
Dalton Trans ; 41(8): 2486-99, 2012 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-22222360

RESUMO

The variable chelating behavior of 3-methoxysalicylaldehyde-4(N)-substituted thiosemicarbazones was observed in equimolar reactions with [PdCl(2)(PPh(3))(2)]. The new complexes were characterized by various analytical, spectroscopic techniques (mass, (1)H-NMR, absorption, IR). All the new complexes were structurally characterized by single crystal X-ray diffraction. Crystallographic results showed that the ligands H(2)L(1) and H(2)L(4) are coordinated as binegative tridentate ONS donor ligands in the complexes 1 and 4 by forming six and five member rings. However, the ligands H(2)L(2) and H(2)L(3) bound to palladium in 2 and 3 as uninegative bidentate NS donors by forming a five member chelate ring. From this study, it was found that the substitution on terminal 4(N)-nitrogen may have an influence on the chelating ability of thiosemicarbazone. The presence of hydrogen bonding in 2 and 3 might be responsible for preventing the coordination of phenolic oxygen to the metal ion. The interaction of the complexes with calf-thymus DNA (CT-DNA) has been explored by absorption and emission titration methods. Based on the observations, an electrostatic binding mode of DNA has been proposed. The protein binding studies were monitored by quenching of tryptophan and tyrosine residues in the presence of complexes using Lysozyme as model protein. Antibacterial activity studies of the complexes have been screened against pathogenic bacteria such as Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa. MIC50 values of the complexes showed that they exhibited significant activity against the pathogens and among them, 3 exhibited higher activity. Further, anticancer activity of the complexes on the lung cancer cell line A549 has also been studied.


Assuntos
Aldeídos/química , DNA/metabolismo , Nitrogênio/química , Compostos Organometálicos/metabolismo , Compostos Organometálicos/farmacologia , Paládio/química , Tiossemicarbazonas/química , Animais , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Transporte Biológico , Bovinos , Linhagem Celular Tumoral , Humanos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular , Muramidase/metabolismo , Compostos Organometálicos/química , Ligação Proteica , Relação Estrutura-Atividade
14.
Metallomics ; 4(1): 101-13, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22051854

RESUMO

The coordination propensities of 4(N,N')-diethylaminosalicylaldehyde-4(N)-substituted thiosemicarbazones (H(2)L(1-4)) were investigated by reacting with an equimolar amount of [PdCl(2)(PPh(3))(2)]. The new complexes were characterized by various spectroscopic techniques. The structure determination of the complexes [Pd(DeaSal-tsc)(PPh(3))] (1), [Pd(DeaSal-mtsc)(PPh(3))] (2) and [Pd(DeaSal-etsc)(PPh(3))] (3) by X-ray crystallography showed that ligands are coordinated in a dibasic tridentate ONS donor fashion forming stable five and six membered chelate rings. The binding ability of complexes (1-4) to calf-thymus DNA (CT DNA) has been explored by absorption and emission titration methods. Based on the observations, an electrostatic and an intercalative binding mode have been proposed. The protein binding studies have been monitored by quenching of tryptophan and tyrosine residues in the presence of complexes using lysozyme as a model protein. As determined by MTT assays, complex 3 exhibited a higher cytotoxic effect towards human lung cancer cell line (A549) and liver cancer cells (HepG2). LDH, NO assay and cellular uptake of the complexes have been studied. Further, antibacterial activity studies of the complexes have been screened against the pathogenic bacteria such as Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa, MIC50 values of the complexes showed that the complexes exhibited significant activity against the pathogens and among the complexes, 3 exhibited higher activity.


Assuntos
Antibacterianos , Bactérias/efeitos dos fármacos , DNA/química , Compostos Organometálicos , Paládio/química , Tiossemicarbazonas/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Linhagem Celular Tumoral , Cristalografia por Raios X , DNA/metabolismo , Humanos , Ligação de Hidrogênio , Ligantes , Dados de Sequência Molecular , Estrutura Molecular , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Paládio/farmacologia , Ligação Proteica , Tiossemicarbazonas/farmacologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-21216187

RESUMO

A new series of new hetero-bimetallic complexes containing iron and ruthenium of the general formula [RuCl(CO)(B)(EPh3)(L)] (where E=P or As; B=PPh3, AsPh3, py or pip; L=ferrocene derived monobasic bidentate thiosemicarbazone ligand) have been synthesized by the reaction between ferrocene-derived thiosemicarbazones and ruthenium(II) complexes of the type [RuHCl(CO)(B)(EPh3)2] (where E=P or As; B=PPh3, AsPh3, py or pip). The new complexes have been characterized by elemental analyses, IR, electronic, NMR (1H, 13C and 31P), EXAFS (extended X-ray absorption fine structure spectroscopy) and cyclic voltammetric techniques. Antibacterial activity of the new complexes has been screened against Escherichia coli, Vibrio cholerae, and Pseudomonas aeruginosa species.


Assuntos
Arsenicais/farmacologia , Técnicas Eletroquímicas/métodos , Compostos Ferrosos/química , Compostos Organofosforados/farmacologia , Rutênio/farmacologia , Tiossemicarbazonas/farmacologia , Espectroscopia por Absorção de Raios X , Antibacterianos/química , Antibacterianos/farmacologia , Arsenicais/química , Escherichia coli/efeitos dos fármacos , Ligantes , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Compostos Organofosforados/química , Pseudomonas aeruginosa/efeitos dos fármacos , Bases de Schiff , Espectroscopia de Infravermelho com Transformada de Fourier , Tiossemicarbazonas/química , Vibrio cholerae/efeitos dos fármacos
16.
Metallomics ; 3(1): 42-8, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21132183
17.
J Young Pharm ; 3(4): 259-66, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22224031

RESUMO

The aim of the present investigation was to prepare extended release film coated matrix tablets of cephalexin using binary mixture of two grades of hydrophilic polymer, hydroxypropyl methyl cellulose (HPMC), by direct compression method. Results of the preliminary trials indicated that the polymers used have significant release retarding effect on the formulation. To study the effect of concentration of polymers on drug release from matrix tablets, 3(2) full factorial design was applied. The concentration of HPMC K15M and HPMC 15cps were used as independent variables, while percentage drug release was selected as dependent variable. The dissolution data were fitted into zero-order, first-order, Higuchi and Korsemeyer-Peppas models to identify the pharmacokinetics and mechanism of drug release. Comparative study of dissolution profile of final batch F3 with market preparation (Sporidex AF 375) was done by similarity factor (f(2)) determination and it was concluded that final formulation F3 (10% HPMC K15M, 17.5% HPMC 15cps) shows good similarity with the market product. The results of the accelerated stability study of final formulation F3 for 1 month revealed that storage conditions were not found to have made any significant changes in final formulation F3. The release of cephalexin was prolonged for 6 h by using polymer combinations of HPMC and a twice daily matrix tablet was formulated.

18.
Eur J Med Chem ; 43(2): 268-73, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17513020

RESUMO

New complexes of Pd(II) with N-substituted thiosemicarbazone (1)-(3) have been synthesised and characterised by elemental analyses, IR, electronic, (1)H NMR spectroscopies. The electrochemical behaviour of the complexes has been tested by using cyclic voltammetry. The crystal structures of the complexes have been determined by single crystal X-ray diffraction technique. In all the complexes the thiosemicarbazone ligand is coordinated to palladium through ONS mode. The complex 1 crystallises in the monoclinic space group P2(1)/c with two molecules per unit cell, has the dimensions of a=9.4390(19)A, b=10.645(2)A, c=13.668(3)A, alpha=90 degrees , beta=91.43 degrees and gamma=90 degrees . The complex 3 crystallises in the monoclinic space group P2(1)/c with four molecules per unit cell, has the dimensions of a=14.119(3)A, b=11.155(2)A, c=18.503(4)A, alpha=90 degrees , beta=112.02 degrees and gamma=90 degrees . The new complexes have been tested for their antibacterial activity against various pathogenic bacteria. From this study, it was found out that the activity of the complex 2 almost reaches the effectiveness of the conventional bacteriocide Streptomycin.


Assuntos
Paládio/química , Paládio/farmacologia , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Cristalografia por Raios X , Eletroquímica , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier
19.
Artigo em Inglês | MEDLINE | ID: mdl-17182271

RESUMO

Complexes of the type [Ru(CO)(EPh(3))(B)(L)] (E = P or As; B = PPh(3), AsPh(3), py or pip; L=dianion of the Schiff bases derived from thiosemicarbazone with acetoacetanilide, acetoacet-o-toluidide and o-chloro acetoacetanilide) have been synthesized from the reactions of equimolar amounts of [RuHCl(CO)(EPh(3))(2)(B)] and Schiff bases in benzene. The new complexes have been characterized by analytical and spectral (IR, electronic, NMR) data. The arrangement of PPh(3) groups around ruthenium metal was determined from (31)P NMR spectra. An octahedral structure has been assigned for all the new complexes. All the complexes exhibited catalytic activity for the oxidation of benzyl alcohol and cyclohexanol in presence of N-methylmorpholine-N-oxide as co-oxidant. The complexes also exhibited antibacterial activity against E. coli, Aeromonas hydrophilla and Salmonella typhi. The activity was compared with standard streptomycin.


Assuntos
Arsênico/química , Nitrogênio/análise , Oxigênio/análise , Rutênio/análise , Enxofre/análise , Aeromonas/metabolismo , Anti-Infecciosos/farmacologia , Benzeno/química , Catálise , Escherichia coli/metabolismo , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana/métodos , Oxigênio/química , Rutênio/química , Salmonella typhi/metabolismo , Bases de Schiff , Espectrofotometria/métodos , Estreptomicina/análise , Tiossemicarbazonas/química
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 65(3-4): 678-83, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16546440

RESUMO

New hexa-coordinated ruthenium(III) complexes of the type [RuX(2)(EPh(3))(2)(L)] (E=P or As; X=Cl or Br; L=monobasic bidentate Schiff base derived from the condensation of benzhydrazide with furfuraldehyde, 2-acetylfuran and 2-acetylthiophene) have been synthesized from the equimolar amounts of [RuX(3)(EPh(3))(3)] or [RuBr(3)(PPh(3))(2)(MeOH)] and Schiff bases in benzene. The new complexes have been characterized by analytical, spectral (IR, electronic and EPR), magnetic moment, and cyclic voltammetry. An octahedral structure has been tentatively proposed. All the complexes have exhibited catalytic activity for the oxidation of benzyl alcohol, cyclohexanol and cinnamylalcohol in the presence of N-methylmorpholine-N-oxide as co-oxidant. All the new complexes were found to be active against the bacteria such as E. coli, Pseudomonas, Salmonella typhi and Staphylococcus aureus. The activity was compared with standard Streptomycin.


Assuntos
Antibacterianos/química , Benzamidas/química , Furanos/química , Compostos Organometálicos/química , Rutênio/química , Tiofenos/química , Antibacterianos/síntese química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Catálise , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/farmacologia , Análise Espectral
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