Design, synthesis, in silico studies, and antidiabetic activity of several sulfanilamide incorporated 2,3-disubstitut-ed thiazolidin-4-ones

A panel of 2,3-disubstituted thiazolidin-4-ones 4a-n was synthesised from Schiff bases 3a-n derived from sulfanilamide, by reaction with thioglycolic acid. The compounds were characterised by means of IR, NMR, and Mass spectral data. Compounds 4a-n were screened for DPPH scavenging assay and compounds 4e, 4h, 4i, and 4n exhibited moderate activity. Compounds 4e, 4h, and 4i were tested at 200 mg/kg and 4e at 50 mg/kg b.w. orally for antidiabetic activity in fructose induced diabetic rats. They exhibited significant antidiabetic activity compared to the control group. Pioglitazone was used as a standard drug. The tested compounds exhibited better and ignificant serum cholesterol lowering activity when compared with the control and standard groups. They also reduced the triglyceride level after the 21st day; however, it was insignificant when compared to the control group. Compound 4n displayed the highest binding energy when docked with PPAR-γ followed by compounds 4e, 4h, and 4i when compared to pioglitazone. The physicochemical, drug likeness and ADME properties of the title compounds were found to be satisfactory.

Se sintetizó un panel de tiazolidinas-4-onas 2,3-disustituidas 4a-n a partir de las bases de Schiff 3a-n derivadas de la sulfanilamida por reacción con ácido tioglicólico. Los compuestos se caracterizaron por IR, RMN y datos espectrales de masa. Los compuestos 4a-n se analizaron para DPPH y los compuestos 4e, 4h, 4i y 4n mostraron una actividad moderada. Los compuestos 4e, 4h y 4i se probaron a 200 mg/kg y 4e a 50 mg/kg b.w. oralmente para la actividad antidiabética en ratas diabéticas, inducida por fructosa. Los compuestos mostraron una actividad antidiabética muy significativa en comparación con el grupo control. La pioglitazona se utilizó como fármaco estándar. Los compuestos ensayados mostraron una mejor y significativa actividad reductora del colesterol sérico en comparación con los grupos control y estándar. Estos compuestos también redujeron el nivel de triglicéridos después del 21° día, aunque fue insignificante en comparación con el grupo control. El compuesto 4n mostró la mayor afinidad de unión cuando se acopló a PPAR-γ, seguido de 4e, 4h y 4i en comparación con la pioglitazona. Las propiedades fisicoquímicas, la similitud con el fármaco y las propiedades ADME de los compuestos fueron satisfactorias, lo que los convierte en útiles agentes antidiabéticos.

Um painel de 2,3-disubstituído thiazolidina-4-ones 4a-n foram sintetizados a partir de bases Schiff 3a-n derivado da sulfanilamida por reacção com ácido tioglicólico. Os compostos eram caracterizado por IR, NMR e dados espectrais de massa. Os compostos 4a-n foram rastreados para O ensaio DPPH de limpeza radical e os compostos 4e, 4h, 4i e 4n exibiram actividade moderada. Os compostos 4e, 4h e 4i foram testados a 200 mg/kg e 4e a 50 mg/kg de peso corporal por via oral para antidiabéticos. actividade em ratos diabéticos induzidos por frutose. Exibiram uma actividade antidiabética altamente significativa actividade em comparação com o controlo. A pioglitazona foi utilizada como droga padrão. Os compostos testados exibiu uma melhor e significativa actividade de redução do colesterol sérico quando comparado comde triglicéridos após o 21° dia; no entanto, foi insignificante quando comparado com o controlo. O composto 4n mostrou a maior afinidade de ligação quando acoplado com PPAR-γ seguido de 4e, 4h, 4i quando comparado com pioglitazona. O propriedades físico-químicas, de semelhança com drogas e ADME dos compostos do título de propriedade também foram encontrados paraser satisfatórios, tornando-os agentes antidiabéticos úteis.

A descrição matemática da detecção eletroanalítica dos íons de zinco em formas farmacêuticas de uso oftálmico, baseada na complexação de zinco com algumas bases de Schiff / The mathematical description for the electroanalytical detection of zinc ions in ophthalmic pharmaceutical forms, based on zinc complexation with some Schiff bases

RESUMO Um processo eletroanalítico da detecção quantitativa dos íons de zinco bivalente sobre as novas bases de Schiff no modo galvanostático tem sido simulado teoricamente. O respectivo modelo matemático tem sido desenvolvido e analisado mediante a teoria de estabilidade linear e da análise de bifurcações. Foi estabelecido que o sistema é eficiente tanto do ponto de vista eletroanalítico, como do ponto de vista eletrossintético, por ser facilmente estabilizado o estado estacionário. Todavia, o comportamento oscilatorio, neste sistema é mais provável que no caso clássico do desempenho de sensores, baseados em polímeros condutores e outros materiais orgânicos, por haver influências na dupla camada elétrica, causadas pela reação química da formação de complexo.

SUMMARY An electroanalytical process of the quantitative determination of bivalent zinc ions over the novel Schiff bases in galvanostatic mode has been theoretically simulated. The correspondent mathematical model has been developed and analyzed by means of linear stability theory and bifurcation analysis. It was shown that the system is efficient from both electroanalytical and electrosynthetical points of view, as the steady-state is easily stabilized. Nevertheless, the oscillatory behavior in this system is more probable than in the classic case of the sensors, based on conducting polymers and other organic materials, as there are double electric layer influences, caused by complex formation.

Screening and Evaluation of Antioxidant Activities of Selected Naphthalene Compounds / Jurnal Sains Kesihatan Malaysia

@#The antioxidant activities of twelve naphthalene compounds containing (E)-1-((3-iodophenylimino)methyl) naphthalen2-ol(NAPH1), (E)-1-((3-bromophenylimino) methyl) naphthalen-2-ol (NAPH2), E)-1-((4-bromo-2-(trifluoromethoxy)phenylimino) methyl) naphthalen-2-ol, (E)-1-((4-bromo-2-(trifluoromethoxy) phenylimino) methyl)naphthalen-2-ol(NAPH3), (E)-1-((2-methoxy-5-(trifluoromethyl) phenylimino) methyl) naphthalen-2-ol (NAPH4), (E)-1-((naphthalen-2-ylimino) methyl) naphthalen-2-ol (NAPH5), (E)-1-((2-bromo-3-methylphenylimino) methyl) naphthalen-2-ol (NAPH6),(E)-N-((2-ethoxynaphthalen-1-yl)methylene)-3-methylaniline (NAPH7), (E)-4-ethoxy-N-((2-ethoxynaphthalen-1-yl)methylene) aniline (NAPH8), (E)-N-((2-ethoxynaphthalen-1-yl) methylene) naphthalen-1-amine (NAPH9), (E)-1-(2,5-difluorophenyl)-N-((2-ethoxynaphthalen-1-yl) methylene) methanamine (NAPH10), (E)-N-((2-ethoxynaphthalen-1-yl)methylene)-4-fluoroaniline (NAPH11), (E)-N-((2-ethoxynaphthalen-1-yl)methylene)-2-ethylaniline (NAPH12) wereinvestigated in vitro by antioxidant activity (phosphomolybdenum assay), reducing power, H2O2 scavenging activity,metal chelating effects and lipid peroxidation. Scavenging activities of the naphthalen compounds were tested against1,1-diphenyl-2-picrylhydrazyl, hydroxyl and superoxide anion radicals. Most of them are potent antioxidant, radicalsuperoxide anion scavengers and in vitro inhibition of lipid peroxidation. The compounds; NAPH5, NAPH10 and NAPH12were found to exhibit promising antioxidant profiles at 10 and 50 mM concentrations. Among these, NAPH5 at higherconcentration was the most active compound in inhibiting lipid peroxidation as shown in the homogenates of kidney,heart and spleen. The presented results validate that NAPH5, NAPH10 and NAPH12 can be possessed as a source ofantioxidant potential and a rich source of synthetic antioxidant for medicinal or foods.

Vanillin Schiff bases: Molecular interactions in methanol and THF solutions / Bases de Schiff de vainillina: interacciones intermoleculares en soluciones de metanol y THF

SUMMARY Density, ultrasonic velocity and viscosity of some vanillin Schiff bases derivatives have been studied in methanol and tetrahydrofuran (THF) at 308.15 K. From the experimental data, various acoustical parameters such as isentropic compressibility (κ s), Rao's molar sound function (R m ), Van der Waals constant (b), relaxation strength (r), intermolecular free length (L f ), apparent molar compressibility, etc. have been evaluated, which helps in understanding the molecular interactions occurring in these solutions.

RESUMEN En este trabajo se estudiaron la densidad, la velocidad ultrasónica y la viscosidad de soluciones de algunas bases de Schiff derivadas de la vainillina en metanol y tetrahidrofurano (THF) a 308,15 K. A partir de los datos experimentales, se evaluaron diversos parámetros acústicos, como la compresibilidad isentrópica (k s ), la función acústica molar de Rao (R m ), la constante de Van der Waals (b), la fuerza de relajación (r), la longitud intermolecular libre (L f ), la compresibilidad molar aparente, etc., todo lo cual ayuda a comprender las interacciones moleculares que ocurren en estas soluciones.

Two novel Co(II) complexes with two different Schiff bases: inhibiting growth of human skin cancer cells

Using two flexible Schiff bases, H2L1 and H2L2, two new cobalt II (Co(II))-coordination compounds, namely, Py3CoL1 (1) and Py3CoL2 (2) (Py=pyridine, L1=3,5-ClC6H2(O)C=NC6H3(O)-4-NO2, L2=3,5-BrC6H2(O)C=NC6H3(O)-4-NO2) have been synthesized under solvothermal conditions. Single crystal X-ray structural analysis revealed that compounds 1 and 2 are both six-coordinate in a distorted octahedral geometry, and the 1D chain structure was formed by the π…π and C-H…O interactions or C-H…Cl interaction. The in vitro antitumor activities of 1, 2 and their corresponding organic ligands Py, L1, and L2 were studied and evaluated, in which three human skin cancer cell lines (A-431, HT-144 and SK-MEL-30) were used in the screening tests.

Synthesis, characterization and antibacterial screening of some Schiff bases derived from pyrazole and 4-amino antipyrine / Síntesis, caracterización y evaluación antibacteriana de algunas bases de Schiff derivadas de pirazol y 4-amino antipirina

Some Schiff bases of pyrazole and 4-amino antipyrine have been synthesized. The antibacterial screening of these synthesized compounds was done in dimethyl forma-mide against four Gram positive bacteria viz. Bacillus cereus, Staphylococcus aureus, Staphylococcus epidermidids and Micrococcus luteus, and three Gram negative bacteria viz. Proteus mirabilis, Escherichia coli and Klebsiella aerogenes. It is observed that in comparison to Schiff bases of 4-amino antipyrine, pyrazole Schiff bases are better for inhibition for these selected Gram positive and Gram negative bacterial strains.

Se sintetizaron algunas bases de Schiff a partir de pirazol y 4-amino antipirina. La evaluación de la actividad antibacteriana de estos compuestos en dimetil formamida se realizó frente a cuatro bacterias Gram positivas, Bacillus cereus, Staphylococcus aureus, Staphylococcus epidermidids y Micrococcus luteus, y frente a tres bacterias Gram negativas, Proteus mirabilis, Escherichia coli y Klebsiella aerogenes. Se observó mejor inhibición bacteriana frente a las diferentes cepas para las bases de Schiff basadas en pirazol comparadas con aquellas basadas en 4-amino antipirina.

Synthesis, Characterization and Antimicrobial Activities of Some Novel Heterocyclic Schiff Bases.

A series of heterocyclic schiff bases have been synthesised by the condensation of 2-amino-4,6- dimethyl benzothiazole and selected heterocyclic α- hydroxy aldehyde and α-hydroxy ketones. The structures of the products were confirmed by spectral analysis (IR, 1H NMR, 13C NMR and Mass). All the newly synthesized compounds were screened for their antibacterial and antifungal activity against different fungal and bacterial strains.

Synthesis, Characterization and Screening of Some Schiff Bases as Potential Antimicrobial Agents.

Schiff bases derived from 4-amino antipyrene were prepared, and IR and NMR spectral analysis characterized their structure. The Schiff bases produced were (1) 4-((4-chlorobenzylidine)amino)- 1,5-dimethyl-1H-pyrazole-3(2H)-one. [SBS-1], (2) 4-((4-hydroxybenzylidine)amino)-1,5-dimethyl- 1H-pyrazole-3(2H)-one. [SBS-2], (3)1,5-dimethyl-2phenyl-4-((3- phenylallylidine)amino) -1Hpyrazole- 3(2H)-one. [SBS-3], (4)4-((4-hydroxy-3-methoxybenzylidine)amino)-1,5- dimethyl-1Hpyrazole- 3(2H)-one. [SBS-4], (5) 4-(benzylidineamino)-1,5 -dimethyl-1H-pyrazole-3(2H)-one. [SBS- 5], (6) 4-((furan-2-ylmethelene)amino)-1,5-dimethyl-1H-pyrazole-3(2H)-one. [SBS-6] and (7) 4-((4- methoxybenzylidine)amino)-1,5- dimethyl-1H-pyrazole-3(2H)-one. [SBS-7]. The antibacterial activity was studied against S. subfava NCIM 2178, B. megaterium ATCC 9885, P. pseudoalcaligenes ATCC 17440, P. vulgaris NCTC 8313, C. freundii ATCC 10787 and E. aerogenes ATCC 13048. The antibacterial activity was done using Agar Ditch method. The antibacterial activity was evaluated in two polar solvents DMSO and DMF. A differential effect of the compounds extracted in a particular solvent (DMSO/DMF) inhibited different bacteria to a different level. It supports the earlier conclusion that antibacterial activity is dependent on molecular structure of the compound, solvent used and the bacterial strain under consideration. However, from the present results, it appears that cinnamaldehyde as side chain with 4-amino antipyrene as central ligand and DMF as a solvent to be best in inhibiting the studied bacterial strains.

Synthesis, characterization and anticancer studies of some morpholine derived Schiff bases and their metal complexes.

This paper reported series of complexes and their modes of coordination. The series consist of N,N’,O-donor Schiff base formed by condensation reaction of 2-hydroxyacetophenone with 4-(2-aminoethyl)morpholine. The ligand and complexes were characterized by elemental analysis, FT-IR, NMR and UV/Visible spectroscopy. The complexes showed moderate cytotoxicity mediated on MCF-7 breast cancer cell line and were selective to some extent when compared to the WRL68 normal liver cell line.

Design, synthesis and evaluation of Schiff bases & thiazolidinone derivatives for anticonvulsant activity.

A series of 2-oxo-N'-phenylmethylidene-2H-chromene-3-carbohydrazides and their thiazolidinone derivatives were designed on the basis of pharmacophoric distance mapping study of well established anticonvulsant drugs. In another computational study, pharmacokinetic parameters of designed compounds were predicted using Molinspiration Online Property Calculation Toolkit. Structures of all the compounds were confirmed by spectroscopical data. Compounds were evaluated for neurotoxicity by rotorod test. Anticonvulsant activity of test compounds was evaluated by maximal electroshock seizure (MES) animal model of seizures. Test compounds CS-6 and CST-6 were found to possess potent anticonvulsant activity and served as the prototype molecules of the series.

Antimicrobial, Genotoxic and Acute Toxic Effects of Newly Synthesized N-Pyridine Schiff Base Derivatives.

Nine N-pyridine Schiff bases (1-9) that were synthesized by reacting different ortho-, meta- and ortho-metasubstituted salicylaldehyde and 3,5-substituted aminopyridine were evaluated for their antimicrobial activity. The acute in vivo toxicity and genotoxic activity of these compounds were also tested. All of the compounds exhibited antimicrobial activity against Gram-positive (Bacillus cereus, Listeria monocytogenes, Staphylococcus aureus and S. epidermidis) and Gram-negative bacteria (Citrobacter freundii, Enterobacter aerogenes, Escherichia coli, Proteus vulgaris and Salmonella typhimurium) and against yeasts (Candida albicans, C. glabrata, C. utilis, Pichia membranafaciens and Rhodotorula rubra). The minimum inhibitory concentrations (MICs) of the compounds ranged from 0.95 to 1000 μg/ml. For the yeasts tested, the MICs ranged from 0.97 to 250 μg/ml. Compounds 1-6, which were substituted with CH3, NO2, Br and Cl, showed especially significant inhibitory activity against C. albicans, and the MICs of these compounds ranged from 0.97 to 7.81 μg/ml. An in vivo brine shrimp (Artemia salina) acute toxicity assay was used to determine the LD50 values of the test compounds. The LD50 (24 h) values of these compounds ranged from 31.64 to 94.9 μg/ml. Additionally, according to umu-test results, none of the tested compounds showed a genotoxic effect over a range from 10 to 5000 μg/ml.

Synthesis, Characterization and Antimicrobial Activities of Schiff bases of 2-amino-4-(O-chloroanilino)-1, 3-thiazole.

A novel series of schiff bases of 2-amino-4-(o-chloro anilino)-1, 3-thiazole (3a-3j) were synthesized and screened for their antibacterial and antifungal activities. The structures of these compounds were ascertained by UV, IR, 1H NMR, mass spectra and elemental analysis. The antibacterial activity of the synthesized schiff bases were evaluated against Gram positive bacteria such as Staphylococcus aureus, Bacillus subtilis and Gram negative bacteria like Escherichia coli and Klebsiella pneumonia. All the compounds had shown moderate to significant antibacterial activity amongst them; compound 3e exhibited more significant activity against the tested bacteria. The antifungal activity was screened against two strains of fungi such as Candida albicans and Aspergillus niger. Similar to antibacterial activity compound 3e exhibited significant antifungal activity. The standard drugs Amoxycillin and Amphotericin B were used to screen antibacterial and antifungal activity at 10μg/ml respectively. Interestingly compound 3e had shown more prominent inhibitory activity against the tested bacteria and fungi.

Hepatoprotective effect of acetone semicarbazone on Ehrlich ascites carcinoma induced carcinogenesis in experimental mice

<p><b>OBJECTIVE</b>To determine the hepatoprotective effect of acetone semicarbazone (ASC) in vivo in normal and Ehrlich ascites carcinoma (EAC) bearing male Swiss albino mice.</p><p><b>METHODS</b>Drug-induced changes in biochemical and behavioral parameters at dose of 2.0 mg/kg body weight for 14 d and nullifying the toxicity induced by EAC cells were studied. The histopathology studies of the protective effects of ASC on vital organs were also assessed.</p><p><b>RESULTS</b>The administration of ASC made insignificant changes in body weight and behavioral (salivation, diarrhea, muscular numbness) changes during treatment period due to minor toxicity were minimized after the treatment in normal mice. The biochemical parameters, including serum glutamate pyruvate transaminase, glutamate oxaloactate transaminase, alkaline phosphatase, serum glucose, cholesterol, urea, triglyceride and billirubin changed modestly in normal mice receiving ASC. Though the treatment continued, these values gradually decreased to normal level after the treatment. In EAC bearing mice, the toxic effects due to EAC cells in all cases were nullified by treatment with the ASC. Significant abnormalities were not detected in histology of the various organs of the normal mice treated with ASC.</p><p><b>CONCLUSIONS</b>ASC can, therefore, be considered safe in formulating novel anticancer drug, as it exhibits strong protective effect against EAC cell bearing mice.</p>

Hepatoprotective effect of acetone semicarbazone on Ehrlich ascites carcinoma induced carcinogenesis in experimental mice

Objective:To determine the hepatoprotective effect of acetone semicarbazone (ASC) in vivo in normal and Ehrlich ascites carcinoma (EAC) bearing male Swiss albino mice. Methods:Drug-induced changes in biochemical and behavioral parameters at dose of 2.0 mg/kg body weight for 14 d and nullifying the toxicity induced by EAC cells were studied. The histopathology studies of the protective effects of ASC on vital organs were also assessed. Results:The administration of ASC made insignificant changes in body weight and behavioral (salivation, diarrhea, muscular numbness) changes during treatment period due to minor toxicity were minimized after the treatment in normal mice. The biochemical parameters, including serum glutamate pyruvate transaminase, glutamate oxaloactate transaminase, alkaline phosphatase, serum glucose, cholesterol, urea, triglyceride and billirubin changed modestly in normal mice receiving ASC. Though the treatment continued, these values gradually decreased to normal level after the treatment. In EAC bearing mice, the toxic effects due to EAC cells in all cases were nullified by treatment with the ASC. Significant abnormalities were not detected in histology of the various organs of the normal mice treated with ASC. Conclusions: ASC can, therefore, be considered safe in formulating novel anticancer drug, as it exhibits strong protective effect against EAC cell bearing mice.

Synthesis, characterization, and biological applications of some 2-acetylpyridine and acetophenone derivatives.

This paper comprises two series of complexes which showed different modes of coordination. The fist series involved an N,N’,N”-donor Schiff base ligand from the reaction of 2-acetylpridine as carbonyl compound with N,N’-dimethylethylenediamine (L1), the second series involved N,N’,O-donor Schiff base from the condensation reaction of 2-hydroxyacetophenone (ketone) as carbonyl compound with N,N’-dimethylethylenediamine (L2). The ligands and complexes were characterized by using melting point, elemental analysis, FT-IR, NMR, and UV/Visible spectroscopy. The complexes showed very low cytotoxicity towards MCF-7 breast cancer cell line. They also showed moderate zone inhibition against Gram positive bacterium Methicillin-resistant Staphylococcus aureus, Acinetobacter baumannii and Pseudomonas aeruginosa. No antimicrobial activity observed with Klebsiella pneumonia.

DNA binding and cytotoxicity of newly synthesized schiff base (z)-4-(((2-hydroxy phenyl) amino) (phenyl) methylene)-3-methyl-1-phenyl-1hpyrazol-5(4H)-one and its analogues.

A novel Schiff base (Z)-4-(((2-hydroxy phenyl)amino)(phenyl)methylene)-3-methyl-1-phenyl-1Hpyrazol- 5(4H)-one and its analogues were synthesized by condensation of 5-methyl-2-phenyl-4-substituted pyrazolin- 3-one with 2-amino phenol from alcoholic solution.Schiff base ligands arecharacterizedby IR, UV, NMR, elemental analysis and single crystal X- ray diffraction analysis. These potential ligands are subjected to DNA binding analysis against the Calf thymus DNA, their binding constant values were calculated and compared to the standard ruthenium intercalators. The cytotoxic natureof these Schiff base ligands was also studied with the human breast cancer cell line MCF-7 and their IC50 values were determined.

Synthesis, characterization, antimicrobial activities and DNA–binding studies of some Ru (III) complexes of schiff bases.

A new ruthenium (III) Schiff base complexes of the type [RuX2 (PPh3)2(L)] (where X = Cl or Br; L = monobasic bidentate Ligand) have been synthesized. All the complexes were characterized by analytical, IR, electronic and EPR spectral studies. An octahedral geometry has been tentatively proposed to all the new complexes. Further the ligands and complexes were subjected to antimicrobial activity studies. The new complexes have been tested to find out the DNA – binding by electronic spectral studies and anti cancer effect.