Functionalized alkyl and aryl diselenides as antimicrobial and antiviral agents: synthesis and properties.

The different dialkyl and diaryl diselenides with carbamoyl and sulfamoyl moieties 2, 3, 5 and other substituents in the ortho position of benzene ring 4, 7, 8 as well as derivatives of 1,2,4-benzoselenadiazine (6) were designed as antiviral and antimicrobial agents and synthesized. Some of them, particularly 8a and 8b, were found in the antiviral assay in vitro to be strong inhibitors of cytopathic activity encephalomyocarditis virus (EMCV). The compound 4a and 8a were found to have a broad spectrum of acivity against bacteria, yeasts and pathogenic fungi in vitro.

Simultaneous induction of interferon gamma and tumor necrosis factor alpha by different seleno-organic compounds in human peripheral blood leukocytes.

Ebselen is known as anti-inflammatory and anti-oxidant selenium containing drug. We have synthetized 13 seleno-organic compounds, analogs of ebselen. Seven of them were found to be inducers of interferon gamma (IFN-gamma) and/or tumor necrosis factor alpha (TNF-alpha) in human peripheral blood leukocytes (PBL) cultures. The most active cytokine inducers were: 2-phenyl-1,2-benzisoselenazol-3(2H)-one (1, ebselen), bis [2-(N-phenylcarbamoyl)]phenyl diselenide (7) and bis (2-[N-(2-pyridyl)carbamoyl])phenyl diselenide (8). The amounts of IFN and TNF produced by PBL cultures in response to the seleno-organic compounds were found to be similar to that induced by phytohemagglutinin (PHA). The activities of the seleno-organic compounds were dose-dependent and related to the chemical structure of the drugs suggesting involvement of the specific cytokine-inducer receptor. The simultaneous inductions of IFN-gamma and TNF-alpha were highly correlated, but independent on each other.

Organoselenides as potential immunostimulants and inducers of interferon gamma and other cytokines in human peripheral blood leukocytes.

A number of organoselenium compounds have been described as anti-inflammatory, antioxidant, glutathione peroxidase-like agents and inhibitors of prostaglandin synthesis. Here we report that bis [2-(N-phenyl-carboxamido)]phenyl diselenide, 2-phenyl-1,2-benzisoselenazol-3(2H)-one (Ebselen) and related compounds are inducers of interferon gamma (IFN-gamma) and tumor necrosis factor (TNF) in human peripheral blood leukocytes. The IFN and TNF response was rapid, occurring within 20 h, and high--up to 1000 and 2000 units ml-1--and was clearly related to the dosage and the structure of the compounds. The action of the compounds and phytohemagglutinin was synergistic. The IFN gamma and TNF production was reduced after removing adherent cells. Although the mode of action of the compounds is not known, they appear to interact directly or indirectly with both adherent and non-adherent leukocytes, and stimulate the synthesis of a set of different cytokines including factors controlling the cell proliferation. Therefore, organoselenides may be regarded as the biological response modifiers.

The cytotoxic activity of heterologous anti-L-1210 antibodies conjugated with quinones.

Biological effects of conjugates of quinone derivatives with antibodies were studied. Two methods of conjugation of aziridine derivatives of quinone with anti-L-1210 antibodies were used: the direct substitution of the protein amino groups or thiolation of immunoglobulins and subsequent substitution of the sulfhydryl groups introduced. The reactions were carried out in 10% solutions of DMF at pH 8.3-8.9. The biological activity of conjugates, in vitro, was controlled using L-1210 and HeLa cells by measuring the inhibition of incorporation of labeled thymidine. The growth of L-1210 cells was more strongly inhibited by conjugates prepared with anti-L-1210 antibodies than by conjugates with nonimmune IgG. No difference in biological activity was found between conjugates prepared from anti-L-1210 antibodies and normal IgG in tests with HeLa cells.