Drugs online research references
J Med Chem. 1988 Jun;31(6):1205-9.
Synthesis and hypolipidemic activity of 2-substituted isobutyric acid derivatives.
Morishita S, Saito T, Hirai Y, Shoji M, Mishima Y, Kawakami M.
Research Laboratories, Kyushin Pharmaceutical Co., Ltd., Tokyo, Japan.
A series of 2-substituted isobutyric acid derivatives have been synthesized and evaluated as hypolipidemic agents. Compounds 11 and 20 were found to decrease the level of plasma total cholesterol in experimental hyperlipidemic rats to a greater extent than clofibrate (CF) and to increase the level of plasma high-density lipoprotein cholesterol to the same extent as gemfibrozil (GF). Increase in liver weight caused by these compounds were less than those with CF and GF.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3163736&dopt=Abstract
J Exp Med. 1992 Nov 1;176(5):1439-47.
Gemfibrozil enhances the listeriacidal effects of fluoroquinolone antibiotics in J774 macrophages.
Rudin DE, Gao PX, Cao CX, Neu HC, Silverstein SC.
Department of Physiology and Cellular Biophysics, Columbia University, New York, New York 10032.
J774 macrophage-like cells express organic anion transporters that promote the efflux of fluoroquinolone antibiotics such as norfloxacin (NFX) from these cells. Gemfibrozil (GFZ) blocks organic anion transport in J774 cells, thereby facilitating the intracellular accumulation of NFX (Cao, C., H.C. Neu, and S.C. Silverstein. 1991. J. Cell Biol. 115:467a [Abstr.]). To determine whether GFZ enhances the efficacy of fluoroquinolone antibiotics against intracellular bacterial pathogens, J774 cells were infected with Listeria monocytogenes and incubated in medium containing a fluoroquinolone antibiotic in the presence or absence of GFZ. Intracellular growth of L. monocytogenes was evaluated by lysing J774 cells and assaying for colony-forming units of Listeria. GFZ intensified the bacteriostatic effect of 4 micrograms/ml NFX and rendered 8 micrograms/ml bactericidal for L. monocytogenes. GFZ had a similar potentiating effect when used in combination with 2 micrograms/ml ciprofloxacin (CFX). CFX plus GFZ was bactericidal for intracellular L. monocytogenes. Treatment of J774 cells with NFX plus GFZ markedly reduced the cytotoxic effect of the bacteria on these cells. Over 55% of cells treated with 8 micrograms/ml NFX alone were dead 16 h after infection, whereas only 5% of cells treated with 8 micrograms/ml NFX plus GFZ were dead at 16 h. Similarly, GFZ potentiated the ability of 2 micrograms/ml to protect J774 cells against the cytocidal effect of Listeria. NFX in combination with GFZ limited cell-to-cell spread of L. monocytogenes. In antibiotic-free medium, > 99% of J774 cells contained intracellular L. monocytogenes at 14 h after infection. NFX alone in the medium did not change this outcome. However, 4 micrograms/ml NFX plus GFZ decreased bacterial spread by approximately 40% at 24 h postinfection, and 8 micrograms/ml NFX plus GFZ prevented all spread beyond the initially infected cell population. These results suggest that GFZ could be used clinically to enhance the efficacy of fluoroquinolone and of other anionic antibiotics against bacteria that grow and/or reside within macrophages and/or other cells.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1402686&dopt=Abstract
Biochem Pharmacol. 1992 Feb 4;43(3):639-44.
Differential inhibition of long-chain acyl-CoA hydrolases by hypolipidemic drugs in vitro.
Sanchez RM, Alegret M, Adzet T, Merlos M, Laguna JC.
Departamento de Farmacologia y Quimica Terapeutica, Facultad de Farmacia, Universidad de Barcelona, Spain.
The effect of in vitro addition of three hypolipidemic drugs (clofibric acid, bezafibrate and gemfibrozil) on rat palmitoyl-CoA hydrolases has been studied, by using a spectrophotometric method (Berge RK, Biochim Biophys Acta 574: 321-333, 1979) optimized for valoration of crude enzyme preparations. Mitochondrial and microsomal hepatic palmitoyl-CoA hydrolase activities were inhibited by the three drugs in a concentration-dependent fashion. The order of inhibitory potency was gemfibrozil greater than bezafibrate greater than clofibric acid, irrespective of the enzyme activity tested. Cytosolic rat brain palmitoyl-CoA hydrolase activity was not affected. Kinetic studies with gemfibrozil on the solubilized microsomal palmitoyl-CoA hydrolase activity point to a mixed non-competitive type of inhibition.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1347213&dopt=Abstract
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