Securinine induced apoptosis in human leukemia HL-60 cells. (1/19)

AIM: To study whether securinine might induce apoptosis in human leukemia HL-60 cells. METHODS: Inhibition of proliferation was measured using MTT assay. The amount of apoptotic cells was measured by flow cytometry. DNA fragmentation was visualized by DNA agarose gel electrophoresis and the cellular changes were observed by electron microscope. RESULTS: Securinine 5-80 mg.L-1 elicited typical apoptosis morphological changes and DNA fragmentation in a concentration-dependent manner in HL-60 cells. Securinine inhibited HL-60 cell proliferation in a time- and concentration-dependent manner. The IC50 and 95% confidence limits were 27 (15-47) mg.L-1 after 12-h treatment with securinine. CONCLUSION: Securinine induced apoptosis in HL-60 cells.  (+info)

Preparation of new nitrogen-bridged heterocycles. 51. Syntheses and structures of compounds having two indolizine nuclei in a molecule. (2/19)

New compounds having two indolizine nuclei in a molecule were prepared in low to moderate yields from the reactions of potassium 2-indolizinethiolates with 1,omega-dihalides such as 1,2-diiodoethane, 1,3-dibromopropane, 1,4-dibromobutane, alpha,alpha'-dichloro-o-xylene, and alpha,alpha'-dichloro-p-xylene. Most of the products had the conformation in which the two indolizine rings in the molecule are as remote as possible, but only 1,2-bis[[(2-indolizinyl)thio]methyl]benzene derivatives, prepared from potassium 2-indolizinethiolates and alpha,alpha'-dichloro-o-xylene, showed a weak attractive interaction between the two indolizine nuclei in the X-ray analysis and the nuclear Overhauser and exchange spectroscopy (NOESY) spectrum.  (+info)

Synthesis of amino derivatives of 10-(diphenylmethylene)-4-azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione as potential psychotropic and/or anti HIV agents. (3/19)

A series of amino derivatives of 10-(diphenylmethylene)-4-azatricyclo[5.2.1.0(2.6)]dec-8-ene-3,5-dione, analogues of chlorpromazine and aminoperazine have been prepared. These compounds are expected to have antipsychotic and/or anti HIV activity. Molecular structure of III was confirmed by an X-ray structure analysis. The cytotoxicity and anti HIV activity of derivatives I-IV were determined.  (+info)

Synthesis of oxiran-2-ylmethyl and oxiran-2-ylmethoxy derivatives of some 4-azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-diones as potential beta-adrenolytics. (4/19)

A series of aminoalkanol derivatives of 10-(diphenylmethylene)-4-azatricyclo[5.2.1.0(2.6)]dec-8-ene-3,5-dione and 4-hydroxy-4-azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione have been prepared. The pharmacological profile of selected compounds was evaluated for their affinities at beta-adrenoceptors. The investigated compounds exhibit modest affinity for these receptors.  (+info)

Securinine, a GABAA receptor antagonist, enhances macrophage clearance of phase II C. burnetii: comparison with TLR agonists. (5/19)

Innate immune cell stimulation represents a complementary approach to vaccines and antimicrobial drugs to counter infectious disease. We have used assays of macrophage activation and in vitro and in vivo phase II Coxiella burnetii infection models to compare and contrast the activity of a novel innate immune cell agonist, securinine, with known TLR agonists. As expected, TLR agonists, such as LPS (TLR4) and fibroblast-stimulating lipopeptide-1 (FSL-1; TLR2), induced macrophage activation and increased macrophage killing of phase II C. burnetii in vitro. FSL-1 also induced accelerated killing of C. burnetii in vivo. Securinine, a gamma-aminobutyric acid type A receptor antagonist, was found to induce TLR-independent macrophage activation in vitro, leading to IL-8 secretion, L-selectin down-regulation, and CD11b and MHC Class II antigen up-regulation. As seen with the TLR agonists, securinine also induced accelerated macrophage killing of C. burnetii in vitro and in vivo. In summary, as predicted by the literature, TLR agonists enhance macrophage killing of phase II C. burnetii in vitro, and at least for TLR2 agonists, this activity occurs in vivo as well. Securinine represents a novel macrophage agonist, which has similar effects as TLR agonists in this model yet apparently, does not act through known TLRs. Securinine has minimal toxicity in vivo, suggesting it or structurally similar compounds may represent novel, therapeutic adjuvants, which increase resistance to intracellular pathogens.  (+info)

Preparation of new nitrogen-bridged heterocycles. 60. Syntheses and conformational analyses of bis(indolizin-1-yl) disulfides. (6/19)

Some bis(indolizin-1-yl) disulfides, readily obtainable from the treatment of 1-(benzoylthio)indolizines with piperidine, were prepared and their conformations were investigated. In comparison with those of 1-(benzoylthio)indolizines, the (1)H-NMR spectra of these disulfides showed considerable high field shifts (delta 0.13-0.82 ppm) on each pyridine ring proton and the UV spectra exhibited significant bathochromic and hyperchromic shifts. These results supported strongly the participation of an intramolecular pi-pi interaction between the two indolizine rings in these molecules and, hence, of a particular gauche (cis) conformation. However, the conformational considerations and molecular calculations (Mopac PM3) for some bis(indolizin-1-yl) disulfides showed the presence of four more stable gauche forms in which two are enantiomeric, resulting in three types of gauche structures. These three types of gauche structures were confirmed by X-ray analyses.  (+info)

Enantioselective total syntheses of nankakurines A and B: confirmation of structure and establishment of absolute configuration. (7/19)

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Stereocontrol in N-directed hydroboration: synthesis of amino alcohols related to the piperidine alkaloids. (8/19)

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