The Hypolipidemic Activity of Boronated Nucleosides in Male Mice and Rats

Burnham, Bruce S.; Sood, Anup; Tomasz, J.; Powell, Wilson M.; Spielvogel, Bernard F.; Chen, S. Y.; Hall, Iris H.

doi:10.1155/mbd.1996.173

Cited by 3 publications

(4 citation statements)

References 4 publications

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“…The drugs did not appear to increase fecal excretion of lipids, but decreased appetite and reduced activity of ratelimiting enzymes for de novo lipid synthesis, i.e., cytoplasmic acetyl CoA synthetase, squalene synthetase, and phosphatidylate phosphohydrolase, with IC 50 values of approximately 10 -5 M [61]. The cyanoborane adduct of 3'-amino-2',3'-dideoxythymidine demonstrated potent hypolipidemic activity in CF 1 mice and Sprague-Dawley rats at 8 mg/kg/day [62]. The boronated nucleoside lowered rat serum chylomicron and VLDL cholesterol levels while increasing serum HDL cholesterol levels after 14 days.…”

Section: -Phenylpiperidine-carbomethoxyborane Tetramethylammonium Domentioning

confidence: 99%

Synthesis and Pharmacological Activities of Amine-Boranes

Burnham¹

2005

CMC

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A number of amine-boranes and related derivatives possess a wide range of biological activities including antineoplastic, antiviral, hypolipidemic, anti-inflammatory activities, anti-osteoporotic and dopamine receptor antagonist activities. The compounds include borane complexes of alpha-amino acids, aromatic, aliphatic and heterocyclic amines, and nucleosides. The syntheses of amine-borane derivatives are generally carried out by first preparing a tertiary amine- or phosphine-cyano- or carboxyborane to serve as a borane donor for a subsequent Lewis acid exchange reaction. Borane adducts of simple aliphatic amines, heterocyclic amines and nucleic acids demonstrated potent cytotoxic activity in vitro and in vivo against murine and human tumor models. These boron-containing compounds were shown to inhibit DNA synthesis; such inhibition was caused primarily by reducing de novo purine biosynthesis via inhibition of PRPP amidotransferase, IMP dehydrogenase and dihydrofolate reductase activities. Aliphatic, heterocyclic and nucleoside amine-boranes have also been shown to possess hypolipidemic activity in mice and rats. Many boron derivatives from different chemical classes demonstrated both cytotoxic and hypolipidemic activities. They decreased low-density lipoprotein (LDL) cholesterol while increasing high-density lipoprotein (HDL) cholesterol levels. The mode of action of these compounds in the 50-100 microM concentration range appeared to be by increasing lipid excretion from the body and by inhibiting rate-limiting enzyme activities for the de novo synthesis of lipids and cholesterol (e.g., phosphatidylate phosphohydrolase, ATP-dependent citrate lyase, cytoplasmic acetyl coenzyme A [CoA] synthetase, HMG CoA reductase, and acetyl CoA carboxylase). Selected amine-boranes (e.g., trimethylamine-cyanoborane, N-methylmorpholine-cyanoborane, and the base-boronated 2'-deoxynucleosides) have anti-inflammatory, analgesic, anti-arthritic and anti-osteoporotic activities.

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Section: -Phenylpiperidine-carbomethoxyborane Tetramethylammonium Domentioning

confidence: 99%

Synthesis and Pharmacological Activities of Amine-Boranes

Burnham¹

2005

CMC

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“…after 14 days upon completion of the study. Body weights, organ weights and daily food consumption of rats were determined as previously reported [22].…”

Section: -(4'-methoxyphenacyl)-34-bis(4'-methoxyphenyl)-1h-pyrrolementioning

confidence: 99%

“…Compactin, also an HMG-CoA reductase inhibitor, has been shown to inhibit the growth of murine L929 cells [21]. Likewise, a number of amine-boranes [22][23][24][25][26][27][28], 2,3-dihydrophthalazine-l,4-diones [29], sesquiterpene lactones [30], and 1,2,4-triazolidine-3,5-diones [31] have demonstrated such crossover between cytotoxic and hypolipidemic properties. …”

Section: Introductionmentioning

confidence: 99%

Lipid-Lowering Effects of Ethyl 2-Phenacyl-3-aryl-1H-pyrrole- 4-carboxylates in Rodents

et al. 2004

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-A series of substituted 2-phenacyl-3-phenyl-1H-pyrrole-4-carboxylates were prepared from substituted acetophenones in 6 steps. The final condensations between a chloroenal and an aminoketone were carried out under neutral conditions in parallel to yield the series listed below. Selected pyrrole derivatives proved to be potent hypolipidemic agents lowering serum triglyceride concentrations in CF-1 male mice after 14 days of I.P. administration. One agent orally lowered serum cholesterol in Sprague-Dawley male rats at 2mg/kg/day after 14 days. The agents demonstrated a lowering of mouse serum LDLcholesterol levels and selected compounds showed an elevation of serum HDL-cholesterol levels. The cholesterol concentrations in the liver were raised while the cholesterol and triglyceride contents of the aorta were significantly lowered by the selected trisubstituted pyrrole.

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“…Previously with the boron analogues of o-amino acids, i.e amine-carboxyboranes, heterocyclic amine boranes and 2'deoxynucleoside boranes other biological activities, e.g. hypolipidemic [7][8][9][10][11][12][13], antiarthritic, antiinflammatory, antiosteoporoeous [14][15][16][17][18][19] have been demonstrated in rodents. The present investigation involved the examination of boronated aromatic amino acids as potent hypolipidemic or anti-inflammatory agents in mice at 8 mg/kg, I.P.…”

Section: Introductionmentioning

confidence: 99%

The Hypolipidemic and Anti‐Inflammatory Activity of BoronatedAromatic Amino Acids in CF₁ Male Mice

Miller

Sood²,

Spielvogel³

et al. 1999

Metal-Based Drugs

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The boronated aromatic amino acids were shown to be potent hypolipidemic agents in mice lowering both serum cholesterol and triglycerides after 16 days. Selective compounds were as effective as the clinical standards. Furthermore, the compounds were effective anti-inflammatory agents reducing local and central pain as well as suppressing LPS induced endotoxic shock in mice. These agents inhibited lysosomal and proteolytic enzymes of the liver and macrophages as a part of their mechanism of action.

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The Hypolipidemic Activity of Boronated Nucleosides in Male Mice and Rats

Cited by 3 publications

References 4 publications

Synthesis and Pharmacological Activities of Amine-Boranes

Synthesis and Pharmacological Activities of Amine-Boranes

Lipid-Lowering Effects of Ethyl 2-Phenacyl-3-aryl-1H-pyrrole- 4-carboxylates in Rodents

The Hypolipidemic and Anti‐Inflammatory Activity of BoronatedAromatic Amino Acids in CF₁ Male Mice

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The Hypolipidemic Activity of Boronated Nucleosides in Male Mice and Rats

Cited by 3 publications

References 4 publications

Synthesis and Pharmacological Activities of Amine-Boranes

Synthesis and Pharmacological Activities of Amine-Boranes

Lipid-Lowering Effects of Ethyl 2-Phenacyl-3-aryl-1H-pyrrole- 4-carboxylates in Rodents

The Hypolipidemic and Anti‐Inflammatory Activity of BoronatedAromatic Amino Acids in CF1 Male Mice

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The Hypolipidemic and Anti‐Inflammatory Activity of BoronatedAromatic Amino Acids in CF₁ Male Mice