Kadriye Benkli

Synthesis and antifungal activities of some aryl(benzofuran-2-yl)ketoximes

In this study, some aryl(benzofuran-2-yl)ketoximes and their ethers and esters were synthesised. The structure elucidation of the compounds was performed by IR, 1H NMR and mass spectroscopic data and elemental analyses results. Antifungal activities of the compounds were examined and notable activity was obtained.

Synthesis and antifungal activities of some aryl (3-methyl-benzofuran-2-yl) ketoximes

In this study, some aryl (3-methyl-benzofuran-2-yl) ketoximes and their ethers and esters were synthesised. 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.

Synthesis and characterization of a new macrocyclic ligand and its copper (II), cadmium (II), and lead (II) complexes : Genotoxic activity of these complexes in cultured human lymphocytes

A new macrocyclic ligand 1,1′-bis(bis-(6,6′-oxymethylenyl-2,2′-bipyridine) binaphthyl, (L), and its complexes CuL(ClO4)2, CuL(NO3)2·3H2O, CdL(ClO4)2, and PbL(ClO4)2 have been synthesized and characterized on the basis of IR, 1H NMR, 13C NMR, FAB mass, and elemental analyses. Genotoxicity of these metal complexes has also been investigated by cytokinesis-blocked micronucleus assay in cultured human lymphocytes. Blood cultures were set up from two healthy donors, and treatment was done with different test concentrations for 24 and 48 h. The current results indicate that all compounds caused cytotoxicity by decreasing the cell number at the 150 μg/mL doses for 48-h treatments. On the other hand, CuL(ClO4)2, CuL(NO3)2·3H2O and PbL(ClO4)2 exhibited genotoxicity by inducing the number of micronucleated cells at doses of 150 μg/mL for 24-h treatments, but CdL(ClO4)2 did not significantly alter micronucleus induction. Hence, some test compounds may act as mutagens or produce clastogenic effects depending upon their chemical structures.

Studies on the cytotoxic, apoptotic and antitumoral effects of Au(III) and Pt(II) complexes of 1, 10-phenanthroline on V79 379A and A549 cell lines

In the present study, Au(III) and Pt(II) complexes of 1, 10-phenanthroline (phen) were synthesized and used as the test compounds. The structure elucidation of the synthesized compounds was performed by IR, 1H-NMR and MASS spectroscopic data and the results of elemental analyses. The cytotoxic and apoptotic effects of test compounds were elucidated on V79 379A (Chinese hamster lung fibroblast like) and A549 (human lung carcinoma epithelial like) cell lines. Cytotoxicity was measured with MTT assay and antitumoral effect was determined by colony forming ability methods. In addition, nuclear fragmentation and activation of apoptotic enzyme (caspase-3) and DAPI staining were used to detect the apoptotic effect of the compounds. All the test compounds induced time and concentration-dependent cytotoxic and antitumoral effects. Significant increases in the levels of apoptosis were observed with increasing exposure concentration.

Synthesis and antimicrobial activities of some new nitroimidazole derivatives

In this study, some new nitroimidazole derivatives were obtained from 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethylamine dihydrochloride (4) and 1-(2-bromoethyl)-2-methyl-5-nitroimidazole (5), which were prepared using metronidazole. Compound 4 was reacted with arylisothiocyanates (6) to obtain 1-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-3-arylthioureas (7) and the latter with α-bromoacetophenones (8) to give 3-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-2-arylimino-4-aryl-4-thiazolines (9). Also 1-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-2-phenyl-4-arylideneimida-zolin-5-ones (11) were prepared by reaction of 4 with 2-phenyl-4-arylidene-5-oxazolones (10). The reaction of the other starting material 5 with 5-arylidenethiazolidin-2,4-dione (12) gave 3-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-5-arylidenethiazolidin-2,4-dione (13) derivatives. Structural elucidation of the compounds was performed by IR,1H-NMR and MASS spectroscopic data and elemental analysis results. Antimicrobial activities of the compounds were examined and moderate activity was obtained.

Modification of intracellular free calcium in cultured F2408 embryo fibroblasts by 3-substituted-2-thiohydantoin derivatives.

3‐substituted‐2‐thiohydantoin derivatives were synthesized and their structures elucidated by IR, 1H‐NMR spectroscopy and elemental analysis. The cytotoxicity of the 2‐thiohydantoin derivatives to rat embryo fibroblasts (F2408) in vitro was determined, and the effects of these compounds on intracellular free Ca2+, [Ca2+]i, were measured by spectrofluorophotometry. Cytotoxicity was determined by metabolic reduction of a tetrazolium salt to a formazan dye (MTT assay). Compounds 4 and 7 showed cytotoxic activity, with IC50values in the range of 1–1.2 μM. Introduction of either chlorophenyl, metoxyphenyl, nitrophenyl or benzyl groups at C‐3 resulted in concentration‐dependent cytotoxic effects. Compounds 1–6 at 1 μM or more significantly increased [Ca2+]iin a dose‐dependent manner in the cultured fibroblasts. This action may have been mediated through intracellular calcium stores.

Gold(III) compounds-mediated inhibition of lung cancer cell proliferation.

Research on chemotherapeutics for lung cancer is crucial for designing a new therapeutic strategy against malignant lung tumors. Although radiotherapy and chemotherapy, which are not selective for cancer cells and exert toxic effects on healthy cells, have a limited advantage, they are the primary treatment modalities for non-small lung cancer. In addition to cytotoxicity, resistance of chemotherapeutics results in failure of treatment. This is why it is of utmost importance to focus on the creation of new chemotherapeutics without toxicity for the successful treatment and improved survival of cancer patients. New gold(III) and Pt(II) compounds were synthesized with a heterocyclic ligand using 2-phenylimidazo[4,5-f][1,10]phenanthroline as a ligand and bis-1,4-di[([1,10] phenanthroline-5-il)amino]-2-buten as a bridge molecule. The characterization of the compounds was carried out using a variety of spectroscopic methods (1H NMR, IR, MS, and elemental analysis). Their antiproliferative, antitumoral, and apoptotic activities were determined. IR spectra and NMR results confirmed the formation of dinuclear heterocyclic complexes for two metal complexes. Cytotoxicity studies on lung cancer cells (A549) and healthy cells (CHL) showed a marked increase in cytotoxicity with the use of gold(III) complexes, and especially [Au(L)B](PF6)2 showed higher cytotoxic and apoptotic features than cisplatin at lower concentrations in cancer cells. These findings have been supported by results from DAPI staining and colorimetric measurement of the caspase-3 enzyme in both cell lines. Compounds showed selective toxicity on the cancer cells. In the light of the high efficacy of our newly synthesized gold complexes, they might be good and promising anticancer agents compared with cisplatin.

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.

Investigation of the pharmacological profiles of dinuclear metal complexes as novel, potent and selective cytotoxic agents against ras-transformed cells

Around the world scientists try to design successful cures against still incurable diseases, especially cancers. New targets for prevention and new agents for therapy need to be identified. We synthesized novel metal complexes [Au(L1)(L2)Pt]Cl2 and [Ru(L1)2(L2)Pt]Cl2 for determining their cytotoxic and apoptotic effects. The complexes are synthesized by using 1,8-diaminonaphthalene (L1), and bis-1,4-di[([1,10]phenanthroline-5-il)aminomethyl]cyclohexane (L2) as ligands. This is the first study to examine these metals and these molecules in cancer treatment. We elucidated the effects of test compounds with embryonic rat fibroblast-like cells (F2408) and H-ras oncogene activated embryonic rat fibroblast-like cancer cells (5RP7). Results showed that our complexes are more effective than cisplatin to kill ras-transformed cells. Although the [Au(L1)(L2)Pt]Cl2 compound showed a cytotoxic potency higher than [Ru(L1)2(L2)Pt]Cl2 against cancer cells, it proved to be almost five times less effective in decreasing cell viability over healthy cells. Au(III) compound selectively targets the cancer cells but not the healthy cells.

Assessment of in vitro cytotoxic and genotoxic activities of some trimethoprim conjugates

Trimethoprim, a commonly used antibacterial agent, is widely applied in the treatment of variety of infections in human. A few studies have demonstrated an extensive exposure of man to antibiotics, but there is still a lack of data for cytotoxic effects including nephrotoxicity, gastrointestinal toxicity, hematotoxicity, neurotoxicity and ototoxicity. The main purpose behind this study was to determine cytotoxic and genotoxic activities of trimethoprim (1), trimethoprim with maleic acid (2) and trimethoprim in conjugation with oxalic acid dihydrate (3). The cytotoxic effects of these three conjugates were elucidated by employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoium bromide (MTT) assay using embryonic rat fibroblast-like cell line (F2408) and H-ras oncogene activated embryonic rat fibroblast-like cancer cell line (5RP7). Additionally, determination of genotoxic activity of these three compounds were studied by using cytokinesis blocked micronucleus assay (CBMN) in human lymphocytes. The results demonstrated that trimethoprim alone and its combination with other compounds are able to induce both cytotoxic and genotoxic damage on cultured cells (F2408, 5RP7, human lymphocytes).