Hypocholesteremic Activity Research Articles

Synthesis and hypocholesteremic activity of aminoacetylenyl linoleates

Synthesis and hypocholesteremic activity of aminoacetylenyl linoleates

Effect of garlic (Allium sativum linn) on serum lipoproteins and lipoprotein cholesterol levels in albino rats rendered hypercholesteremic by feeding cholesterol

The hypocholesteremic activity of garlic was tested by incorporation freeze-dried garlic powder at 0.5, 1.0, 2.0 and 3.0% levels in an atherogenic diet fed to rats. It was observed that 0.5 and 1.0% levels were not effective whereas the other 2 levels were. The group fed 2.0% garlic powder had much lower serum cholesterol level than the one fed 3%. The increased levels of low density lipoproteins (LDL) and LDL-cholesterol in rats fed the atherogenic diet were partly reversed in rats receiving a supplement of 2% garlic powder. On a cholesterol-containing diet, high density lipoprotein (HDL) and HDL-cholesterol levels were decreased. Inclusion of garlic powder in the atherogenic diet enhanced the percentage of HDL whereas no change was observed in HDL cholesterol levels. Commercial garlic pearls (equivalent to 0.15% garlic powder in the diet) produced a significant decrease in serum and liver cholesterol levels in rats fed the atherogenic diet. On the other hand, asafoetida at 1.5% level failed to reduce the serum cholesterol levels in the cholesterol-fed rats.

ChemInform Abstract: EFFECTS OF MOLECULAR MODIFICATION ON HYPOCHOLESTEREMIC ACTIVITY OF 1,3‐BIS(SUBSTITUTED PHENOXY)‐2‐PROPANONES AND RELATED DERIVATIVES

AbstractAus Phenolen entstehen mit Epoxiden die Aroxy‐carbinole (I), die zu den Ketonen (II) oxidiert werden können.

Effects of molecular modification on hypocholesteremic activity of 1,3-bis(substituted phenoxy)-2-propanones and related derivatives.

A series of 1,3-bis(substituted phenoxy)-2-propanones, long-chain ketones, and related derivatives has been synthesized, and it has been found that certain analogues produce significant lowering of serum cholesterol levels in Sprague-Dawley rats. These compounds possess no estrogenic properties and are nontoxic at 10 mg/kg/day. Physical studies on these compounds include an attempt to correlate hypocholesteremic activity with the lipophilic, electronic, and steric properties of the compounds. The 1-octanol-H2O partition coefficient was measured for certain derivatives and the pi constant for the substituents was calculated. Hammett's sigma constants for aromatic substituents were obtained from the literature. The only correlation found to exist is between hypocholesteremic activity and steric size and position of the aromatic substituents in the propanones.

A labelled hypocholesteremic agent, preparation OF 2‐(2‐pyridine)‐1‐(3‐chlorophenyl)‐2‐phenyl‐1‐methylethanol uniformly tritiated on the 2‐phenyl ring

Abstract2‐(2‐Pyridine)‐1‐(3‐chlorophenyl)‐2‐phenyl‐1‐methylethanol (I), containing tritium uniformly distributed in the 2‐phenyl ring, was synthesized in two steps with tritiated benzene as the labelled starting material.An improved procedure was employed for the coupling of m‐chloroacetophenone and 2‐benzylpyridine. The higher melting of two enantiomeric pairs, known for its hypocholesteremic activity in rats, was isolated and found to have a chemical purity of >95% and a specific activity of 0.11 mCi/mmole.

Hypocholesterolemic activity of analogous compounds related to eritadenine, an active component of shiitake, Lentinus edodes Sing (author's transl)

Various kind of compounds related to the hypocholesteremic alkaloid, eritadenine, an active component of Japanese mushroom, Lentinus edodes SING, (Japanese name, Shiituke) were studied concerning structure-activity relationship. Compounds were administered orally to cholesterol-fed rats for 3 days. It may be concluded from the results as follows : 1) Eritadenine esters were found to be 10 times as active as the mother substance in serum cholesterol-lowering activity. 2) Among the 6-substituted analogs, hydroxyamino compound was found to possess a high biological activity, equivalent to that of eritadenine. Thus, basic substituents at the 6-position of the purine ring may be essential for the activity, as evidenced by the loss of activity of the 6-hydroxy, 6-mercapto, 6-chloro, and hydrogen compounds. 3) Dihydroxybutyric acid derivatives, having pyrimidine or other heterocyclic ring, were found to be inactive or less active than eritadenine. From these facts, it seems that presence of a purine ring in the structure is important for cholesterol-lowering activity. 4) Hypocholesteremic effect of eritadenine and its stereoisomers decreased in the following order : D-erythro (natural eritadenine), D-threo, L-erythro, L-threo (no effect). β-Deoxyeritadenine showed a moderate cholesterol-lowering activity, whereas α-deoxyeritadenine was ineffective. These results suggest that dihydroxybutyric acid is required for the potent hypocholesteremic activity, and especially, α-OH group is associated with the activity.

A Comparison of the effects of some hypocholesteremic compounds on squalene metabolism in Tetrahymena pyriformis and rat liver

1. 1. Six dialkylaminoethoxy compounds, five of which exhibit hypocholesteremic activity, have been compared for their effects on the growth of Tetrahymena pyriformis and on the in vitro cyclization of squalene to tetrahymanol by this organism. With one exception, there was good correlation between ability of the compounds to inhibit growth and squalene cyclization. There was also good correlation between inhibition of T. pyriformis squalene cyclase and hypocholesteremic activity. 2. 2. The above compounds have also been compared for their effects on the conversion of 2,3-oxidosqualene to C 30 and C 27, sterols by rat liver homogenate. Only two of the six (one of which did not display hypocholesteremic activity) inhibited this process at the concentrations employed. The effect of these two agents on the conversion of squalene to C 30 and C 27 sterols by rat liver homogenate was also examined. 3. 3. Cholesterol had no effect on either in vivo or in vitro squalene cyclization by T. pyriformis, nor did it overcome the in vitro inhibition of squalene cyclization by 3β-(β-dimethylaminoethoxy)-androst-5-en-17-one (DMAE-DHA). 4. 4. A lag period is associated with tetrahymanol synthesis by a cell-free preparation of T. pyriformis. Two fat-soluble antioxidants inhibited squalene cyclization by this preparation; one water-soluble one did not. Sulfhydryl-blocking agents had little effect on squalene cyclase activity.

N-Aralkyl-piperidyl Carbanilates as Hypocholesteremic Agents

A number of N-aralkyl-N-methylaminoethyl carbanilates have been described in the literature as possessing hypocholesteremic activity. This series of compounds now has been extended to include 12 new o-[1-(substituted benzyl)-4-piperidyl]-N-(sub-stituted phenyl) urethans and six new o-[1-(substituted benzyl)-4-piperidylideneimino]-N-(substituted phenyl) urethans. Two new derivatives of N1-[(1-substituted benzyl)-4-piperidyl]-N3(p-chloro-phenyl)urea have been prepared. Eleven intermediate piperidine derivatives, that have not been previously described in the literature, have been prepared and characterized. Fifteen of these new compounds have been studied for their ability to inhibit the incorporation of mevalonate-2-14C into cholesterol by homogenates of rat liver. Six of the compounds exhibited greater than 50% inhibition when tested at a concentration of 2 × 10−5M. Appreciable incorporation of radioactivity into 7-dehydrocholesterol was observed with these six compounds. No significant reduction in serum cholesterol levels could be found in rats dosed at a level of 40 mg./ kg. of body weight over a period of 7 days.

N-aralkyl-N-methylaminoethyl carbanilates as hypocholesteremic agents

A group of aralkylaminoethyl esters and ureas of substituted carbanilic acids was prepared and studied for hypocholesteremic activity in eucholesteremic mice. Biological results indicated that modification of either terminal aromatic ring altered the activity of the resultant compound. The meta and para methyl substituted carbanilates of aralkylmethylaminoethanol consistently exhibited the most desirable effect. In the dicarbanilate series of aralkyl or aryl substituted iminodiethanols, no appreciable activity was seen.

The Synthesis of Hydroxylamine Derivatives Possessing Hypocholesteremic Activity

The Synthesis of Hydroxylamine Derivatives Possessing Hypocholesteremic Activity

Comparison of in vitro bile acid binding capacity and in vivo hypocholesteremic activity of cholestyramine.

SummaryMethods for in vitro assay of cholate binding capacity and for in vivo assay of hypocholesteremic activity of preparations of cholestyramine, an anion exchange resin, were developed and compared. In the in vitro assay, 20 ml of 0.3 M phosphate buffer at pH 6.0, 20 or 40 mg of the resin and 40 mg of sodium cholate were mixed and shaken for 30 minutes; the filtrates were assayed for cholate spectrophotometrically, and the cholate bound by the resin determined by difference.In the in vivo method, a hypercholesteremic diet was fed to day-old chicks for 2 weeks; graded levels of the anion exchange resin were added to the diet during the second week. Plasma cholesterol levels were then determined as an indicator of the activity of the resin.The relative activities of the various preparations of cholestyramine and other anion exchange resins compared very well when tested by the two methods of assay. Addition of excipients in preparations of cholestyramine for clinical use had no effect on cholate binding...

Studies of the distributions of lipids in hypercholesteremic rats: 3. Changes in hypercholesteremia and tissue fatty acids induced by dietary fats and marine oil fractions

The hypocholesteremic activities of dogfish liver oil and tuna and menhaden oils were duplicated by feeding rats proportionate amounts of the fatty acid components of the oils; neither selachyl alcohol nor the unsaponifiable components of the oils affected the hypercholesteremia of the rats. The relative hypocholesteremic activities of menhaden oil fatty acid ester fractions (I.V. of 48.6–353) were not predictable on the basis of such criteria as their total unsaturation, contents of polyunsaturated fatty acids (PUFA), or contents of more saturated acids. The hypocholesteremic activity of the fraction with an iodine value of 48.6 was similar to that of corn oil (I.V. = 124). Only minor amounts of the linolenate homologues were required to promote significant reductions in the cholesterol contents of the livers in these rats. Rats fed tallow-PUFA mixtures incorporated little of the available PUFA into the cholesterol esters of their tissues. However, a homeostatic mechanism appeared to regulate the incorporation of appreciable and uniform amounts of available PUFA into the plasma phospholipids and myocardia of the rats. The PUFA patterns in the plasma and liver suggested that the preconditioned animals had a partial depletion of the essential fatty acid (EFA) reserves for these tissues. However, a very adequate supply of EFA was apparently available for the myocardial tissues of these same rats. The fractionation of marine oils and some modified methods for lipid analyses are discussed.

THYROMIMETICS. I. THE SYNTHESIS AND HYPOCHOLESTEREMIC ACTIVITY OF SOME 3' AND 3',5'-ALKYL AND ARYL-3,5-DIIODOTHYRONINES.

THYROMIMETICS. I. THE SYNTHESIS AND HYPOCHOLESTEREMIC ACTIVITY OF SOME 3' AND 3',5'-ALKYL AND ARYL-3,5-DIIODOTHYRONINES.

THYROMIMETICS. II. THE SYNTHESIS AND HYPOCHOLESTEREMIC ACTIVITY OF SOME BETA-DIETHYLAMINOETHYL ESTERS OF IODINATED THYROALKANOIC ACIDS.

THYROMIMETICS. II. THE SYNTHESIS AND HYPOCHOLESTEREMIC ACTIVITY OF SOME BETA-DIETHYLAMINOETHYL ESTERS OF IODINATED THYROALKANOIC ACIDS.

Mode of Action of Cholesterol-Lowering Agents

The implication of hypercholesteremia in atherogenesis has stimulated a continued search for cholesterol-lowering agents within the last decades. In addition to various dietary regimens ranging from a glass of orange juice to special formula diets, a great number of drugs ranging from household remedy aspirin (acetylsalicylic acid) to new sophisticated compounds have been reported to possess hypocholesteremic activity. Their efficacy, side-effects, and clinical usefulness will be discussed elsewhere. 1 The present review is confined to the mode of action of unsaturated fats, sitosterol, nicotinic acid, thyroid hormones and analogues, and triparanol. They are selected for discussion because they have been extensively studied clinically and with respect to their mode of action. Since, as will be delineated, these agents act at different sites of the metabolic pathways of cholesterol, several avenues are thus opened for further investigation of cholesterol metabolism and atherogenesis. Unsaturated Fats It has long been known that the