Novel hydrazone derivatives and their tetracoordinated metal complexes

New aroylhydrazone derivatives and their Co(II), Ni(II) and Cu(II) complexes have been synthesized and characterized by means of elemental analyses, molar conductances and magnetic measurements as well as electronic spectra, IR spectra, 1H NMR spectra, 13C NMR spectra and LC mass spectra. Ni(II) complexes were found to have general compositions [ML], where L = 2,6-dipiperidino-4-(2-hydroxybenzylidene hydrazino)-1,3,5-s-triazine; 2,6-dipiperidino-4-(5-bromo-2-hydroxybenzylidenehydrazino)-1,3,5-s-triazine, while other complexes have composition [ML2] (M = Co2+ or Cu2+). The infrared spectra indicate the coordination of imino nitrogen and phenolic oxygen atoms. Tetracoordinated structures are proposed for the Co(II) Ni(II) and Cu(II) complexes on the basis of magnetic evidence and electronic spectra

Synthesis of some novel isoxazolidine derivatives via 1,3-dipolar cycloaddition and their biological evaluation

A series of novel substituted isoxazolidine derivatives were synthesized by 1,3-dipolar cycloaddition reactions of a-aryl-N-methyl nitrones with diethyl maleate. The structures of the synthesized compounds were characterized using spectroscopic methods. All the synthesized compounds were screened for their antibacterial activities against Gram-positive and Gram-negative bacteria and for their antifungal activities against a yeast strain. The results show that all the synthesized compounds displayed significant activity against S. epidermidis, M. luteus, B. cereus, B. abortus and C. albicans when compared to standard drugs. © 2019, Gazi University Eti Mahallesi. All rights reserved

Synthesis of some novel isoxazolidine derivatives via 1,3-dipolar cycloaddition and their biological evaluation

A series of novel substituted isoxazolidine derivatives were synthesized by 1,3-dipolar cycloaddition reactions of a-aryl-N-methyl nitrones with diethyl maleate. The structures of the synthesized compounds were characterized using spectroscopic methods. All the synthesized compounds were screened for their antibacterial activities against Gram-positive and Gram-negative bacteria and for their antifungal activities against a yeast strain. The results show that all the synthesized compounds displayed significant activity against S. epidermidis, M. luteus, B. cereus, B. abortus and C. albicans when compared to standard drugs. © 2019, Gazi University Eti Mahallesi. All rights reserved

fingolimod used in the treatment of multiple sclerosis

Multiple sclerosis (MS) is a very common disease of vital importance. In the MS treatment, some drugs such as fingolimod which help to protect nerves from damage are used. The main goal of the drug therapy in MS is to take control of the inflammation which leads to the destruction of myelin and axons in nerve cell and thus prevent and stop the progression of the disease. Fingolimod (FTY720) is an orally active immunomodulatory drug that has been used for the treatment of relapsing-remitting multiple sclerosis. It is a sphingosine-1-phosphate receptor modulator which prevents lymphocytes from contributing to an autoimmune reaction by inhibiting egress of lymphocytes them from lymph nodes. In this study, we have computer designed, synthesized and characterized two novel derivatives of FTY720, F1-12h and F2-9, and have determined their underlying mechanism of their beneficial effect in SH-SY5Y, SK-N-SH, and U-118 MG cell lines. For this purpose, we first determined the regulation of the cAMP response element (CRE) activity and cAMP concentration by F1-12h and F2-9 together with FTY720 using pGL4.29 luciferase reporter assay and cAMP immunoassay, respectively. Then, we have determined their effect on MS-and GPCR-related gene expression profiles using custom arrays along with FTY720 treatment at non-toxic doses (EC10). It was found that both derivatives significantly activate CRE and increase cAMP concentration in all three cell lines, indicating that they activate cAMP pathway through cell surface receptors as FTY720 does. Furthermore, F1-12h and F2-9 modulate the expression of the pathway related genes that are important in inflammatory signaling, cAMP signaling pathway, cell migration as well as diverse receptor and transcription factors. Expression of the genes involved in myelination was also increased by the treatment with F1-12h and F2-9. In summary, our data demonstrate that the two novel FTY720 derivatives act as anti-inflammatory ultimately by influencing the gene expression via the CAMP and downstream transcription factor CRE pathway. In conclusion, F1-12h and F2-9 might contribute future therapies for autoimmune diseases such as multiple sclerosis. (C) 2016 Elsevier Ltd. All rights reserved