A series of 2-(4-substituted-1-(homo)piperazinyl)benzimidazoles was prepared and tested for H1-antihistaminic activity in vitro and in vivo. Most of the compounds showed antihistaminic activity and some of the 1-[2-(substituted-oxy)ethyl] derivatives exhibited potent activity. In a structure-activity comparison it was found that the oxygen atom in the 2-(substituted-oxy)ethyl group at the 1-position of the benzimidazole nucleus played an important role for potent antihistaminic activity, especially in vivo. One of the most potent compounds, 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole (69), was 39 times more potent than chlorpheniramine maleate in H1-antihistaminic activity in vivo and was selected for clinical evaluation. The structure of compound 69 is of interest because it provides only a single aromatic unit linked through a chain to a basic nitrogen, while most H1-antihistaminic agents have structures that comprise a double-aromatic unit linked through a chain to a basic tertiary amino group.
The lipoperoxide values and glutathione peroxidase activity in blood plasma, along with the glutathione peroxidase, catalase and cupro-zinc superoxide dismutase activities in erythrocytes were investigated in 60 women with Type 2 (non-insulin-dependent) diabetes mellitus and in 71 healthy women. The mean lipoperoxide value and the mean plasma glutathione peroxidase activity in the diabetic patients were significantly higher than those in the control subjects (lipoperoxide p less than 0.001, plasma glutathione peroxidase activity p less than 0.01). The plasma glutathione peroxidase activities did not, however, correlate with the plasma lipoperoxide values. The erythrocyte glutathione peroxidase activity was approximately ten times higher than that of the plasma glutathione peroxidase activity, nor did they correlate with each other. In contrast to the findings of other authors on the activities of the protective enzymes in erythrocytes against oxidative damage, there were no significant differences of erythrocytes glutathione peroxidase, catalase and superoxide dismutase activities between diabetic and control women.
A series of 2-(2-pyridinyl)benzimidazoles was synthesized and evaluated for antiinflammatory activity by the carrageenan-induced rat paw edema assay. Among several active derivatives, 2-(5-ethylpyridin-2-yl)benzimidazole (6) was selected for further study. A comparison of compound 6 with phenylbutazone and tiaramide revealed that 6 possesses stronger activity in acute inflammatory models possibly with slightly less gastrointestinal irritation than both phenylbutazone and tiaramide.
We previously identified a G-rich silencer element involved in negative regulation of catalase gene expression in some hepatoma cells (Mol. Cell. Biol., (1992), 12, 2525-2533). To study a nuclear binding protein for this element, we screened cDNA libraries from a rat ascites hepatoma cell line by binding with a synthetic oligonucleotide probe and obtained several clones. One of them, designated SW, was studied in detail. A clone (SW2) of this series contained a near full length cDNA encoding a putative peptide with 463 amino acid residues. We isolated this peptide as a fusion protein. It was found that the protein strongly bound to the C-stretch of the DNA sequence in a single strand specific fashion, but absolutely did not to G-rich sequence. The protein bound weakly to the corresponding double-stranded DNA as well as to C-rich RNA sequence. This protein, though not the expected one, was found to be a novel protein whose DNA binding domain was located on the region containing at least 75 amino acid residues of the carboxyl terminus. A proline rich region was also observed in the middle part of the protein. Northern blot profiles indicated extensive and slight expression of both 2.0 kb and 2.7 kb mRNA species in some hepatoma cell lines and in the rat liver, respectively.
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