Formulation and characterization studies of inclusion complexes of voriconazole for possible ocular application.

In our study, Voriconazole (VOR) was selected as an active agent to be used for the treatment of ocular fungal infections. To overcome low aqueous solubility of VOR, inclusion complexes with α-cyclodextrin (α-CD), ß-cyclodextrin (ß-CD), γ-cyclodextrin (γ-CD), hydroxypropyl-cyclodextrin (HP-CD), hydroxypropyl-ß-cyclodextrin (HP-ß-CD) hydroxypropyl-γ-cyclodextrin (HP-γ-CD), methyl-ß-cyclodextrin (M-ß-CD) and sulfabutylether-ß-cyclodextrin (SBE-ß-CD) were formulated. Characterization studies revealed that inclusion complexes were formulated successfully with the lyophilization method. Aqueous solubility of VOR was enhanced up to 86 fold with the formation of the inclusion complexes. MTT analyses results revealed the safety of the complexes on 3T3 mouse fibroblast cell lines while Microbroth Dilution Method revealed the remarkable antifungal activities of the complexes. Analyses results revealed that inclusion complexes will overcome the poor ocular bioavailability of VOR resulting inefficient treatment of severe ocular fungal infections.

Cytotoxic and apoptotic effects of boron compounds on leukemia cell line.

In this study we investigated the effects of boric acid and sodium tetraborate on an acute leukemia cell line and healthy human lymphocytes. We evaluated the effects of boric acid and sodium tetraborate on the HL-60 cell line and healthy human lymphocytes by using the methods of MTT, Neutral Red, AO (flow cytometry) and transmission electron microscope. We found that there were dead cells at a concentration of 500 µM boric acid and sodium tetraborate (50 % and 40 %, respectively). An apoptotic effect was found at a concentration of 1,000 µM concentration in normal lymphocytes and HL-60 (acute leukemia cells) cells (2.5 % and 8.8 % respectively). We observed that boric acid at a concentration of 500 µM caused double nucleus and micronucleus formation in both HL-60 cells and lymphocytes. An expansion in mitochondrial dimension and deformation in cristas also appeared. Our findings suggest that boric acid is more effective than sodium tetraborate on the HL-60, and boric acid in particular showed a cytotoxic effect on HL-60 in comparison to healthy lymphocytes and it also affected the mitochondrial pathway.

Synthesis and initial biological evaluation of substituted 1-phenylamino-2-thio-4,5-dimethyl-1H-imidazole derivatives.

In this work, some new 2-[(4,5-dimethyl-1-(arylamino)-1H-imidazol-2-yl)thio]-1-(aryl)ethanone derivatives were synthesized and investigated for their antibacterial, antifungal and anticancer activities. Toxicity of the most effective compounds was established by performing Brine-Shrimp lethality assay. Antifungal activity of the compounds was found to be higher than antibacterial and anticancer activities of the compounds.

Synthesis and biological evaluation of pyrazoline derivatives bearing an indole moiety as new antimicrobial agents.

1-(p-Methylphenyl)-3,5-diaryl-2-pyrazoline derivatives (2a-f) were synthesized via the treatment of 1-(1H-indol-3-yl)-3-aryl-2-propen-1-ones (1a-f) with p-methylphenylhydrazine hydrochloride in hot acetic acid. The structures of these compounds were elucidated by IR, ¹H NMR, and mass spectral data and elemental analysis. These compounds were investigated for their antimicrobial activity. Brine-Shrimp lethality assay was carried out to determine the toxicity of the compounds. Compound 2e, which is the pyrazoline derivative bearing the 2,5-dichlorophenyl moiety, can be identified as the most promising agent against Klebsiella pneumoniae (ATCC 13883) and Candida glabrata (ATCC 36583) due to its inhibitory effects on K. pneumoniae and C. glabrata with a MIC value of 100 µg/mL as a non-toxic agent (LC50 > 1000 µg/mL).

Synthesis and antimicrobial activity of some new hydrazone-bridged thiazole-pyrrole derivatives.

In this work, we synthesized fourteen different compounds which contain hydrazone bridged thiazole and pyrrole rings. For this purpose, pyrrole-2-carboxaldehydes were reacted directly with thiosemicarbazide in ethanol and then obtained thiosemicarbazones were condensed with α-bromoacetophenone derivatives (Hantzsch reaction) to give 1-substituted pyrrole-2-carboxaldehyde [4-(4-substituted phenyl)-1,3-thiazol-2-yl] hydrazones. The structures of the obtained compounds were elucidated by using IR, (1)H-NMR and FAB(+)-MS spectral data and elemental analyses results. All of the compounds were screened for their antibacterial and antifungal activities against twelve different microorganisms by using microbroth dilution method. Ketoconazole and chloramphenicol were used as standard drugs. All of the compounds showed good activity against Staphylococcus aureus and Enterococcus faecalis.

Poly (hydroxyethyl methacrylate-glycidyl methacrylate) films modified with different functional groups: In vitro interactions with platelets and rat stem cells.

Copolymerization of 2-hydroxyethylmethacrylate (HEMA) with glycidylmethacrylate (GMA) in the presence of α-α'-azoisobisbutyronitrile (AIBN) resulted in the formation of hydrogel films carrying reactive epoxy groups. Thirteen kinds of different molecules with pendant NH2 group were used for modifications of the p(HEMA-GMA) films. The NH2 group served as anchor binding site for immobilization of functional groups on the hydrogel film via direct epoxy ring opening reaction. The modified hydrogel films were characterized by FTIR, and contact angle studies. In addition, mechanical properties of the hydrogel films were studied, and modified hydrogel films showed improved mechanical properties compared with the non-modified film, but they are less elastic than the non-modified film. The biological activities of these films such as platelet adhesion, red blood cells hemolysis, and swelling behavior were studied. The effect of modified hydrogel films, including NH2, (using different aliphatic CH2 chain lengths) CH3, SO3H, aromatic groups with substituted OH and COOH groups, and amino acids were also investigated on the adhesion, morphology and survival of rat mesenchymal stem cells (MSCs). The MTT colorimetric assay reveals that the p(HEMA-GMA)-GA-AB, p(HEMA-GMA)-GA-Phe, p(HEMA-GMA)-GA-Trp, p(HEMA-GMA)-GA-Glu formulations have an excellent biocompatibility to promote the cell adhesion and growth. We anticipate that the fabricated p(HEMA-GMA) based hydrogel films with controllable surface chemistry and good stable swelling ratio may find extensive applications in future development of tissue engineering scaffold materials, and in various biotechnological areas.

Antimicrobial activity of a new series of benzimidazole derivatives.

Due to antimicrobial importance of benzimidazoles and hydrazones, some benzimidazole-hydrazone compounds were synthesized to screen their antimicrobial activity. Structures of the synthesized compounds were elucidated by (1)H-NMR, IR and ES-MS spectral data and elemental analysis. The synthesized benzimidazole-hydrazones exhibited very weak antibacterial activity. However, antifungal activity of some of the synthesized compounds was very notable against Candida species. The compounds displaying important antifungal activity were screened for their toxicity. Artemia salina 96-well assay was used to determine cytotoxicity of the compounds. Tested compounds exhibited toxicity to different extents (LD(50) = 126.33-368.72 µg/mL). Nevertheless, determination of 3-14 folds higher LD(50) than minimum inhibitory concentration is a significant finding, which demonstrates that the compounds display antifungal activity at non-toxic concentration.

Antimicrobial activity of a new combination system of benzimidazole and various azoles.

In the present study a new series of benzimidazole derivatives bearing various (benz)azolylthio moieties were synthesized so as to investigate their antimicrobial activity. Structures of the target compounds (5a-5i) were confirmed by their IR, (1) H-NMR, ES-MS spectral data, and elemental analyses. The synthesized compounds (5a-5i) exhibited poor activity against bacterial strains. On the other hand, antifungal activity of the compounds against Candida species was very significant. Brine-Shrimp lethality assay was performed for determination of toxicity of the compounds. Compounds 5a, 5c, and 5d were evaluated as non-toxic in addition to their attractive antifungal activity. However, the other compounds (5b, e-i) in the series showed toxicity to different extents.

Antimicrobial activity and a SAR study of some novel benzimidazole derivatives bearing hydrazone moiety.

In this study 12 novel benzimidazole compounds bearing hydrazone moiety were synthesized in order to investigate their possible antibacterial and antifungal activity. Structures of the synthesized compounds were elucidated by spectral data. Six different gram-negative and four different gram-positive bacterial strains were used in antibacterial activity tests. Antifungal activity tests were also performed against three different fungal strains. Most of the test compounds found to be significantly effective against Proteus vulgaris, Staphylococcus typhimurium, Klebsiella pneumoniae and Pseudomonas aeruginosa gram-negative bacterial strains. A structure-activity relationship (SAR) study including some electronic parameters was carried out and a connection between antibacterial activity and electronic properties of the target compounds was determined. Toxicity of the most effective compounds was established by performing Brine-Shrimp lethality assay.

Investigation of the apoptotic effect of curcumin in human leukemia HL-60 cells by using flow cytometry.

Curcumin (diferuloylmethane), the major yellow pigment isolated from the turmeric (Curcuma longa), has received much attention due to several biological properties. Curcumin exhibits a variety of pharmacological effects including antitumor, anti-inflammatory, and anti-infectious activities. In the present study, the effects of curcumin on apoptosis in the acute promyelocytic human leukemia (HL-60) cells was evaluated. Cytotoxic effects of curcumin on HL-60 cells were determined by MTT. HL-60 cells underwent apoptosis on treatment with curcumin, as indicated by increased annexin V-binding capacity and caspase-3 activation with flow cytometric analysis. Concentrations of 15, 20, and 40 µM curcumin significantly reduced cell proliferations. When HL-60 cells were treated with 10, 15, 20, and 40 µM concentration of curcumin, apoptotic rates were determined as 1.2, 81.1, 84.5, and 88.6%, respectively. On the incubations with the concentrations of curcumin, caspase-3 expressions (+) were found to be elevated by 8.5, 18.6, 91.2, and 92.4%, respectively. It was shown that curcumin had significant cytotoxic and apoptotic effects on HL-60 cells. It was suggested that curcumin may have a potential therapeutic role for human leukemia.

Biosorption of phenol and 2-chlorophenol by Funalia trogii pellets.

The removal of phenol (Ph) and 2-chlorophenol (2-CPh) from aqueous solution by native and heat inactivated fungus Funalia trogii pellets were investigated. The effects of contact time, solid/liquid ratio, optimum pH and temperature on the phenols removal capacity by the pellets were established. The removal efficiency of phenols increased significantly with increasing biomass dose. The optimum pH was detected to be 8.0. The second-order equations are described and evaluated on the basis of a comparative estimation of the corresponding coefficients. The phenol removal equilibrium isotherm was modeled by the Langmuir equations. The enthalpy change values were obtained between -7.62 and -10.64 kJ/mol. This indicated that the uptake of phenols either on native or heat inactivated fungal pellets was based on a physical adsorption process.

Synthesis, antibacterial and antifungal activities of 3-(1,2,4-triazol-3-yl)-4-thiazolidinones.

A new series of 3-(1,2,4-triazol-3-yl)-4-thiazolidinone derivatives has been synthesized by the reaction of Schiff bases of 3-amino-1,2,4-triazoles with mercaptoacetic acid and 2-mercaptopropionic acid. Their antibacterial and antifungal activities were evaluated against S. aureus, S. epidermidis, C. albicans and C. glabrata.

Synthesis and biological activities of new hydrazide derivatives.

The synthesis of a new series of imidazo[1,2-a]pyrazine-2-carboxylic acid arylidene-hydrazides is described. The chemical structures of the compounds were elucidated by IR, (1)H-NMR, FAB(+)-MS spectral data. Their biological activity against various bacteria, fungi species, and Mycobacterium tuberculosis was investigated. Antibacterial activity was measured against Escherichia coli (NRRL B-3704), Staphylococcus aureus (NRRL B-767), Salmonella typhimurium (NRRL B-4420), Proteus vulgaris (NRLL B-123), Enterococcus faecalis (isolated obtained from Faculty of Medicine Osmangazi University, Eskisehir, Turkey), Pseudomonas aeruginosa (NRRL B-23 27853), Klebsiella spp. (isolated obtained from Faculty of Medicine Osmangazi University, Eskisehir, Turkey), while antifungal activity was evaluated against Candida albicans (isolates obtained from Osmangazi Uni. Fac.of Medicine), Candida glabrata (isolates obtained from Osmangazi Uni. Fac.of Medicine). Compounds were also evaluated for antituberculosis activity against Mycobacterium tuberculosis H(37)Rv using the BACTEC 460 radiometric system and BACTEC 12B medium. The compounds showed moderate inhibitor effects against human pathogenic microorganisms., whereas the preliminary results indicated that all of the tested compounds were inactive against Mycobacterium tuberculosis H(37)Rv.

Cytotoxic and genotoxic effects of [Ru(phi)3]2+ evaluated by Ames/Salmonella and MTT methods.

In this work, we synthesized and evaluated the cytotoxic effect of [Ru(phi)(3)](2+), on rat C6 glioma cell line. Cell viability was determined by assay with 3-(4-5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). The mutagenicity of [Ru(phi)(3)](2+) was studied in vitro by using two strains of Salmonella typhimurium with frameshift mutation (TA98) and base-pair substitution mutation (TA100) were used in plate incorporation assay in the absence of metabolic activation. According to the results, the Ru compound is not toxic but mutagenic, and it shows cytotoxic effect towards C6 rat glioma cells in 100 microM.

Synthesis and antifungal activities of some aryl [3-(imidazol-1-yl/triazol-1-ylmethyl) benzofuran-2-yl] ketoximes.

In this study, some aryl [3-(imidazol-1-yl/triazol-1-ylmethyl)benzofuran-2-yl] ketones, aryl (3-methyl-benzofuran-2-yl) ketoximes and aryl [3-(imidazol-1-yl/triazol-1-ylmethyl)benzofuran-2-yl] ketoximes were synthesised starting from 2-aryloyl-3-methyl-benzofuranes. The structure elucidation of the compounds was performed by IR, 1H-NMR, MASS spectroscopy and elemental analyses. Antifungal activities of the compounds were examined and moderate activity was obtained.