3-Chloro-6-[4-(2-pyrid­yl)piperazin-1-yl]pyridazine

In the title compound, C13H14ClN5, the piperazine ring adopts a chair conformation and the dihedral angle between the aromatic rings is 13.91 (7)°. The crystal structure is stabilized by weak inter­molecular C—H⋯N hydrogen-bond inter­actions

EFFECTS OF SOME MICHAEL TYPE ADDITION PRODUCTS ON VARIOUS CYTOKINES

The aim of this research in to investigate the anticytokine activities of the 2-[(2-nitro-l-phenylpropyl)thio]benzoic acid (1), 2-[(2-nitro-l-phenylethyl)thiomethyl]benzimidazole (2) and 2-[(2-nitro-l-phenylpropyl)thiomethyl]benzimidazole (3) derivatives in human primary cells and cell lines. Cytokines are messengers for the regulation of the inflammatory cascades with Tumor Necrosis Factor-a (TNF-a), Interleukin (IL-lβ, IL-2, IL-4 andIL-8), Gamma Interferon (IFN-y) working synergistically. In this study which is performed in cell assay, inhibition capacity of compound 1, 2 and 3 derivatives againts TNF-a, IL-Iβ, IL-8, IL-2, IL-4 and IFN-y production by human whole blood have been measured. The test results were shown that 1, 2 and 3 derivatives have dose-dependent inhibitions on the release of IL-1β, IL-8 and TNF-a in lipopolysaccharide (LPS) stimulated human whole blood and IL-2, IL-4 and IFN-yin phorbolacetate (PHA) stimulated in human whole bloo

3-Chloro-6-{4-[3-(trifluoro­meth­yl)phen­yl]piperazin-1-yl}pyridazine

The title compound, C15H14ClF3N4, was synthesized from 3,6-dichloro­pyridazine and 1-[3-(trifluoro­meth­yl)phen­yl]piper­azine. The piperazine ring is flanked by 3-chloro­pyridazine and 3-trifluoro­methyl­phenyl rings and adopts a chair conformation, whereas the 3-chloro­pyridazine and 3-trifluoro­methyl­phenyl rings are planar, with maximum deviations of 0.0069 (13) and 0.0133 (14) Å, respectively. The crystal structure is stabilized by weak inter­molecular C—H⋯N hydrogen-bond inter­actions

In Vitro Antimicrobial Activities of 6-Substituted-3(2H)- pyridazinone-2-acetyl-2- (substituted/nonsubstitutedbenzal/ acetophenone) Hydrazone Derivatives

Aim: In vitro antibacterial activity of 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(substituted/nonsubstitutedbenzal/ acetophenone) hydrazone derivatives were tested in common species causing hospital-acquired infections. Material and Method: Antimicrobial activities of the compounds were performed by determining minimum inhibitory concentration (MIC) value against four Gram-positive, five Gram-negative and four Candida species fungi. Modified serial microdilution method was carried out. Reference strains of American Type Culture Collection (ATCC) were used. Results: In general, eleven compounds exhibited considerable activity. Comparatively, compound 3 exhibited strong activity against Enterobacter hormaechei and 5, 11 were the most active against Acinetobacter baumannii at 31.25 μg/mL. Compounds 1,2,3,4,8 and 10 were found to be as active as positive control ampicillin trihidrate against Stenotrophomonas maltophilia. On the other hand, compounds 1,2,3,4,7,8,9,10 and 11 showed strong antifungal activitiy as much as fluconazole against Candida tropicalis. Compound 1 was mostly active against Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis. It was also revealed that the antifungal activity of compounds 1, 6, 7, 8 and 9 were higher than the others. Compound 1 and 8 exhibited the best activity against Candida glabrata and Candida parapsilosis respectively. Conclusions: All tested compounds showed better activity against Gram-negative bacteria and yeast than Gram-positive bacteria. These compounds may be considered as alternative antimicrobial agents in the treatment of multiple drug resistant Gram-negative, Gram-positive bacteria and fungal pathogens. Especially, we suggested that Compound 1 and 8 might be a promising candidate of new antifungal agent

SYNTHESIS, CHARACTERIZATION AND DNA INTERACTION OF NOVEL PLATINUM(II) COMPLEXES CONTAINING SUBSTITUTED BENZIMIDAZOLE LIGANDS

WOS: 000403630800004Eight novel Pt(II) complexes corresponding to the following general formula [PtCl2(L-1-L-4)(2)] (C1 -C4) and [PtI2((L1-L4))(2)] (C5-C8) in which 5(6)-chloro/or-methyl-2-H/or-methylbenzimidazole (L-1-L-4) played the key role as carrier ligands were synthesized and characterized by elemental analysis, IR and H-1 NMR. Considering leaving group functions, the anionic ligand iodido and chloro were utilized with the purpose of studying the interaction between the synthesized complexes and pBR322 plasmid DNA by using cisplatin as positive control throughout the Agarose Gel Electrophoresis method. Therefore, looking after plasmid DNA interacting outcomes, synthesized complexes modified the tertiary structure of pBR322 plasmid DNA, and the results showed that the complex C2 ([PtCl2(L-2)(2)]) was highly active compound regarding to all synthesized complexes.Mersin University Scientific Research Funds [2015-TP2-1175]We would like to thank Prof. Dr. Fatma Gumus for her supervision and guidance. This research was financially supported by Mersin University Scientific Research Funds (Grant nos. 2015-TP2-1175)

Investigation of anti- leishmanial activity of the ten different hydrazone derivatives

ULGER, Mahmut/0000-0001-6649-4195WOS: 000378899400006Leishmaniasis is an important parasitic disease in Turkey and the world. Anti-leishmanial drugs such as sodium stibogluconate, miltefosine, paramomycin, amphotericin B, and pentamidine are used for the treatment of leishmaniasis. However, the drugs, used for the chemotheraphy of leishmaniasis, have some side effects such as nephrotoxicity, hepatotoxicity, and teratogenicity. In addition, it is deemed that the discovery and development of the new therapeutic agents must be given priority due to the development of resistance against antimony compounds. The purpose of this study is detecting the anti-leishmanial activity of ten different synthesized hydrazone compounds against Leishmania infantum promastigotes via the microdilution method. The prepared hydrazone compounds, having the concentration of 6 mu g/ml, were added to RPMI-1640 media and the dilution of the hydrazone derivates was performed in the wells of microplates in the range of concentrations of 3 - 0.003 mu g/ml. The microdilution broth method in the microplates was prepared, than the adjusted standard Leishmania infantum promastigotes, 2.5x10(7)cells/mL, were added, into the mentioned microplates which was incubated in 27 degrees C. Twenty h later, the alamar blue were added on the microplates and they were incubated for 4 h. The proliferation of promastigotes was evaluated in 24, 48, and 72 h. It was considered that changing the color from blue to pink in the wells were exhibiting the growth of parasites, while the unchanged color was not. The present study has revealed that the most effective substances against Leishmania infantum promastigotes were 5e, 5g, and 5h compounds (MIC 0.187 mu g/ml) while the least effective compound was 5i (MIC 3 mu g/ml). There is a need for further studies on in vitro activity against the Leishmania amastigotes in macrophages cultures and in vivo experimental animal models for the synthesized compounds showing anti-leishmanial effect in the present study

Cytotoxicity and DNA interactions of some platinum(II) complexes with substituted benzimidazole ligands

UTKU, Semra/0000-0003-3181-9134WOS: 000303330100012PubMed: 22299582In the present study, four Pt(II) complexes with 2-ethyl (1)/or benzyl (2)/or p-chlorobenzyl (3)/or 2-phenoxymethyl (4) benzimidazole carrier ligands were evaluated for their in vitro cytotoxic activities against the human HeLa cervix, oestrogen receptor-positive MCF-7 breast, and oestrogen receptor-negative MDA-MB 231 breast cancer cell lines. The plasmid DNA interactions and inhibition of the BamHI restriction enzyme activities of the complexes were also studied. Complex 3 was found to be more active than carboplatin for all examined cell lines and comparable with cisplatin, except for the HeLa cell line.Research Foundation of Gazi UniversityGazi University [02/2007-16]We would like to thank the Research Foundation of Gazi University (02/2007-16) for financial support

Synthesis, in-vitro cytotoxic activity and DNA interactions of new dicarboxylatoplatinum(II) complexes with 2-hydroxymethylbenzimidazole as carrier ligands

UTKU, Semra/0000-0003-3181-9134WOS: 000343922100009PubMed: 25109360ObjectivesThe aim of this study was to investigate the in-vitro cytotoxic activity of new platinum(II) complexes on the human HeLa (ER-), MCF-7 (ER+) and MDA-MB 231 (ER-) cell lines. Furthermore, we investigated plasmid DNA interactions and inhibition of BamHI and HindIII restriction enzyme activity of the complex 1-4,7. MethodsPlatinum(II) complexes were synthesised from precursor complexes of [PtL2Cl2] and [PtL2I2]. Their cytotoxic activity was tested by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Their plasmid DNA interactions and restriction enzyme activities were also investigated using the agarose gel electrophoresis method. Key findingsThe growth inhibitory effect results showed that the cytotoxicity of complex 2 was found to be the most active complex among the synthesised complexes. ConclusionsThe MTT results showed that complex 2 was found to be cytotoxic equal to cisplatin and higher than carboplatin against the MCF-7 and MDA-MB-231 cell lines. Furthermore, the estrogen or progesterone co-treatment slightly increased the cytotoxicity of complex 2, the cisplatin and carboplatin compared with the complex 2 tested alone in 50m concentration. According to plasmid DNA interaction and the restriction studies, complexes 1-4,7 modified the tertiary structure of pBR322 plasmid DNA, and complexes 2-4 prevented enzyme digestion at high concentrations.Research Foundation of Gazi UniversityGazi University [EF 02/2007-24]This work was supported by Research Foundation of Gazi University (EF 02/2007-24). The authors are grateful to Dr Bahar Tasdelen (Mersin University, Faculty of Medicine Department of Biostatistics and Medical Informatics) for helpful statistical analysis support

Do toxic metals and trace elements have a role in the pathogenesis of conotruncal heart malformations?

Objective: The aim of the present study was to determine the role of toxic elements and trace elements in the pathogenesis of conotruncal heart defects by measuring their concentrations in the first meconium specimens of the affected newborns. Methods: Concentrations of lead, cadmium, iron, zinc, and copper were measured in 1st-day meconium specimens that were collected from 60 newborns with conotruncal heart defects (Group I) and 72 healthy newborns (Group II). Results: The newborns with conotruncal defects and the healthy newborns had statistically similar demographic and clinical characteristics. When compared with healthy newborns, mean concentrations of lead, cadmium, iron, zinc, and copper were significantly higher in newborns with conotruncal heart defects (p = 0.001 for each). In total, 51 newborns with conotruncal heart defects had normal karyotype. These newborns had significantly higher concentrations of lead, cadmium, iron, zinc, and copper when compared with healthy newborns. There were significant and positive correlations between the concentrations of lead and cadmium (r = 0.618, p= 0.001), lead and iron (r= 0.368, p= 0.001), lead and zinc (r = 0.245, p= 0.005), lead and copper (r = 0.291, p= 0.001), cadmium and iron (r = 0.485, p= 0.001), cadmium and zinc (r = 0.386, p= 0.001), and cadmium and copper (r = 0.329, p= 0.001). Conclusion: Toxic metals and trace elements may disturb DNA repair mechanisms by impairing DNA methylation profiles, and thus have a role in the pathogenesis of conotruncal heart defects