Hypolipidemic Activity of Amine‐Borane Aducts of Cyclohexylamineand Toluidine in Rodents

Burnham, Bruce S.; Chen, S. Y.; Sood, Anup; Spielvogel, Bernard F.; Hall, Iris H.

doi:10.1155/mbd.1995.221

Cited by 3 publications

(3 citation statements)

References 15 publications

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“…The agents were shown to decrease rat serum chylomicron and LDL cholesterol levels while increasing serum HDL cholesterol levels after 14 days. The compounds were shown to have the following effects in vitro on the activities of rat hepatic lipid-regulating enzymes: inhibition of phosphatidylate phsphohydrolase, lipoprotein lipase, and neutral cholesterol esterase activities, as well as increasing cholesterol-7α-hydroxylase activity [54].…”

Section: -Methylcyclohexylamine-carboxyboranementioning

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: -Methylcyclohexylamine-carboxyboranementioning

confidence: 99%

Synthesis and Pharmacological Activities of Amine-Boranes

Burnham¹

2005

CMC

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“…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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“…A series of boron containing molecules was found to have anti-hyperlipidemic activity in laboratory animals. Small boronated molecules, such as X -methylamine, ( X = 0−3) boranes, carboxyboranes and cyanoboranes were initially screened showing significant reduction in serum cholesterol levels for carboxyboranes and cyanoboranes. − Compounds with longer substituents on nitrogen − and cyclic nitrogen sites ,,− were also studied, as were ester , and amide 9,10 moieties. Additional hypolipidemic studies were performed on systems containing phosphorus−boron bonds for comparison with B−N structures. ,,, Even as the complexity of the molecules increased, the anti-hyperlipidemic effectiveness of the molecules was quite variable.…”

Section: Introductionmentioning

confidence: 99%

Theoretical Study of the Role of Boron−Nitrogen Dative Bonds in the Physiological Action of Boronated Compounds

et al. 2000

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Some boronated molecules have shown surprising physiological action; however, the mode of action of these compounds is not understood. Our hypothesis is that the boron moiety is attracted to Lewis base sites on an enzyme and the resulting interaction causes an inhibition of the physiological pathway. To study this problem, quantum mechanical calculations of boron−nitrogen bond dissociation energies for 12 molecules have been calculated and compared with physiological activities including anti-hyperlipidemic and anti-neoplastic behavior. Results of linear correlation analysis between bond dissociation energy and physiological action have shown evidence that our hypothesis has merit. Possible locations of enzyme inhibition by boronated compounds are inferred. In addition, structural and energetic features of boronated molecules, including intramolecular electrostatic interactions and Lewis acidity, are discussed.

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Hypolipidemic Activity of Amine‐Borane Aducts of Cyclohexylamineand Toluidine in Rodents

Cited by 3 publications

References 15 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

Theoretical Study of the Role of Boron−Nitrogen Dative Bonds in the Physiological Action of Boronated Compounds

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