A review of studies on the mode of action of clofibrate and betabenzalbutyrate

Fallon, Harold J.; Adams, Larry L.; Lamb, Robert G.

doi:10.1007/bf02532596

Cited by 33 publications

(11 citation statements)

References 29 publications

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“…Further work is necessary before any conclusions can be drawn. The findings of Maragoudakis (26), showing that clofibrate inhibits acetyl-CoA carboxylase, and the findings of Fallon and coworkers (30), showing that clofibrate decreases liver synthesis of sn-glycerol-3-P, may in part account for the hypotriglyceridemic activity of this drug. It also has been suggested that clofibrate alters the release of lipoproteins by liver (31).…”

Section: Sc Ussl Onmentioning

confidence: 85%

Differential effects of benzodioxane, chroman and dihydrobenzofuran analogs of clofibrate in a triton hyperlipemic rat model

Newman

Hellman

Witiak

1973

Lipids

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Clofibrate (ethyl 2‐methyl‐2‐[4‐chlorophenoxy] propionate) is currently an important hypolipemic agent. In this study we describe the biological properties of certain acyclic and cyclic analogs of clofibrate in a hyperlipemic rat model in which the hyperlipemia was induced by ip injection of Triton WR‐1339. Cyclic analogs studied for their hypocholesterolemic and hypotriglyceridemic activities, as well as their ability to modify lipoprotein patterns, include the ethyl esters of 1,4‐benzodioxane‐2‐carboxylic acid, 6‐chlorochroman‐2‐carboxylic acid and 5‐chloro‐2,3‐dihydrobenzofuran‐2‐carboxylic acid. Among the clofibrate analogs, ethyl 6‐chlorochroman‐2‐carboxylate compares most favorably with the parent compound. Whereas the 6‐chlorochroman‐2‐carboxylate is effective as a hypocholesterolemic and hypotriglyceridemic agent, the 1,4‐benzodioxane analog exhibits mainly hypotriglyceridemic activity, while the 2,3‐dihydrobenzofuran analog exhibits hypocholesterolemic activity. Except for the benzodioxane, deschloro analogs are inactive. Results obtained in these studies are discussed in terms of structural requirements for biological activity and modes of action proposed for the parent drug clofibrate.

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Section: Sc Ussl Onmentioning

confidence: 85%

Differential effects of benzodioxane, chroman and dihydrobenzofuran analogs of clofibrate in a triton hyperlipemic rat model

Newman

Hellman

Witiak

1973

Lipids

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“…Certain fibric acid derivatives (clofibrate and bezafibrate) are effective in lowering plasma lipid levels, although the exact mechanism of action remains unclear (Fallon et al, 1972). One mechanism suggests an increased rate of metabolism of triglyceride-rich lipoproteins due to an increase in the activity of lipoprotein lipase by an inhibition of adenylate cyclase activity (Greene et al, 1970).…”

mentioning

confidence: 99%

Effect of the lipid-lowering agent bezafibrate on tumour growth rate in vivo

Mulligan

Tisdale²

1991

Br J Cancer

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Summary The growth rate of the MAC16 tumour in cachectic animals was significantly enhanced by the hypolipidemic agent bezafibrate, while the growth rate of a histologically similar tumour, the MAC13, which grows without an effect on host body compartments was unaffected. Growth of the MAC16 in vitro was unaffected by bezafibrate, suggesting that it was an in vivo phenomenon only. The stimulatory effect of bezafibrate correlated with the maximum plasma levels of free fatty acids (FFA) arising from the catabolism of adipose tissue. Accumulation of '4C-lipid from 1-'4C-triolein administered by intragastric intubation was enhanced in heart, gastrocnemius muscle and tumour of bezafibrate treated animals, while the total lipid absorption did not differ from solvent treated controls. The increased lipid accumulation in the heart, but not the tumour correlated with an increased tissue lipoprotein lipase level. The increased tumour level may arise from an increased uptake of FFA arising from a weakening of the bonds between FFA and albumin. These results suggest that growth of certain tumours is dependent on maintaining sufficient lipid levels and that the lipid mobilising effect of the tumour may be necessary to sustain tumour growth.

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“…that clofibrate antiviral activity is mediated via lipid biogenesis either in the viral envelope or in the host membranes necessary for viral development (6,7). Clofibrate is known to alter cellular lipid metabolism at different levels, suggesting that this drug could deprive replicating viruses of essential lipid components (3,10,14,15,19,20). In addition, Steinhart and associates (18) have demonstrated that clofibrate antiviral activity is directed at some late step in HSV maturation such as during envelopment of the virion by host membranes.…”

mentioning

confidence: 99%

“…The cytotoxic effects of clofibrate and procetofene were determined by monitoring the uptake of macromolecular precursors for deoxyribonucleic acid, protein, and lipid synthesis. The effect of clofibrate and procetofene on uptake of precursors for protein and lipid metabolism was determined because clofibrate is reported to directly affect cell lipid metabolism (3,10,14,15,19,20,23) as well as other metabolic pathways (2,(11)(12)(13) 24 h of any given incubation period. After incubation, cells were trypsinized and collected with a MASH II cell harvester.…”

mentioning

confidence: 99%

Antiviral activity of antilipidemic compounds on herpes simplex virus type 1

Mehl¹,

Witiak²,

Hamparian³

et al. 1980

Antimicrob Agents Chemother

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Two antilipidemic compounds, clofibrate and procetofene, inhibited the replication of herpes simplex virus type 1 (HSV-1) in African green monkey kidney cells. Clofibrate, at a concentration of 400 ,umol/liter caused a 63% reduction (P < 0.001) in HSV-1 yield and at 100 pnol/liter caused a 62% reduction (P < 0.001) in plaque formation. Two stereoisomeric analogs of clofibric acid, (-)-and (+)-desmethyl clofibric acid, also caused a significant inhibition of HSV-1 replication.Procetofene at 5 ,Lmol/liter caused a 56% reduction (P < 0.001) in HSV-1 plaques and at 10 ,umol/liter caused a significant reduction (P < 0.001) in both viral yield (42 to 54%) and plaque formation (65%). Procetofene also inhibited the development of HSV-1 plaques. A concentration of 5 ,umol/liter resulted in a 26% reduction (P < 0.001) in plaque diameter. Because of their nonspecific inhibitory effect on the uptake of cellular macromolecular precursors for nucleic acid and protein biosynthesis, these antilipidemic compounds may exert their antiviral activity by affecting one or more key metabolic host cell pathways.

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A review of studies on the mode of action of clofibrate and betabenzalbutyrate

Cited by 33 publications

References 29 publications

Differential effects of benzodioxane, chroman and dihydrobenzofuran analogs of clofibrate in a triton hyperlipemic rat model

Differential effects of benzodioxane, chroman and dihydrobenzofuran analogs of clofibrate in a triton hyperlipemic rat model

Effect of the lipid-lowering agent bezafibrate on tumour growth rate in vivo

Antiviral activity of antilipidemic compounds on herpes simplex virus type 1

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