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PubMed1997

Significant discrepancies between van't Hoff and calorimetric enthalpies. III.

The study of a wide variety of reversible reactions in solution indicates that the enthalpy, DeltaH(vH), which controls the temperature variation of the equilibrium constant for a reaction, can seldom, if ever, be taken to be independent of the temperature. It is also found in most cases that the values for DeltaH(vH), properly evaluated as varying with the temperature, differ significantly from the values for the enthalpy, DeltaH(cal), determined by direct calorimetry under the same experimental conditions. In a continuing search for reactions which show agreement between DeltaH(vH) and DeltaH(cal), we have studied by isothermal titration calorimetry the reactions of heptylamine with heptanoic acid in dodecane solution and of alpha-cyclodextrin with sodium heptanoate in aqueous solution.

Journal Article↗
PubMed2005

Polyketide double bond biosynthesis. Mechanistic analysis of the dehydratase-containing module 2 of the picromycin/methymycin polyketide synthase.

Picromycin/methymycin synthase (PICS) is a modular polyketide synthase (PKS) that is responsible for the biosynthesis of both 10-deoxymethynolide (1) and narbonolide (2), the parent 12- and 14-membered aglycone precursors of the macrolide antibiotics methymycin and picromycin, respectively. PICS module 2 is a dehydratase (DH)-containing module that catalyzes the formation of the unsaturated triketide intermediate using malonyl-CoA as the chain extension substrate. Recombinant PICS module 2+TE, with the PICS thioesterase domain appended to the C-terminus to allow release of polyketide products, was expressed in Escherichia coli. Purified PICS module 2+TE converted malonyl-CoA and 4, the N-acetylcysteamine thioester of (2S,3R)-2-methyl-3-hydroxypentanoic acid, to a 1:2 mixture of the triketide acid (4S,5R)-4-methyl-5-hydroxy-2-heptenoic acid (5) and (3S,4S,5R)-3,5-dihydroxy-4-methyl-n-heptanoic acid-delta-lactone (10) with a combined kcat of 0.6 min(-1). The triketide lactone 10 is formed by thioesterase-catalyzed cyclization of the corresponding d-3-hydroxyacyl-SACP intermediate, a reaction which competes with dehydration catalyzed by the dehydratase domain. PICS module 2+TE showed a strong preference for the syn-diketide-SNAC 4, with a 20-fold greater kcat/K(m) than the anti-(2S,3S)-diketide-SNAC 14, and a 40-fold advantage over the syn-(2R,3S)-diketide-SNAC 13. PICS module 2(DH(0))+TE, with an inactivated DH domain, produced exclusively 10, while three PICS module 2(KR(0))+TE mutants, with inactivated KR domains, produced exclusively or predominantly the unreduced triketide ketolactone, (4S,5R)-3-oxo-4-methyl-5-hydroxy-n-heptanoic acid-delta-lactone (7). These studies establish for the first time the structure and stereochemistry of the intermediates of a polyketide chain elongation cycle catalyzed by a DH-containing module, while confirming the importance of key active site residues in both KR and DH domains.

Amino Acid Sequence↗
PubMed2001

Dodeca(carboranyl)-substituted closomers: toward unimolecular nanoparticles as delivery vehicles for BNCT.

The syntheses of the dodeca(carboranyl)-substituted closomers, dodeca[7-(2-methyl-1,2-dicarba-closo-dodecaboran-1-yl)heptanoate]-closo- dodecaborate(2-) and dodeca[7-(8-methyl-7,8-dicarba-nido-dodecaboran-7-yl)- heptanoate]-closo-dodecaborate(14-) are reported. These boron-rich, unimolecular nanospheres possess great potential for future use as drug-delivery platforms for boron neutron capture therapy (BNCT).

Boron Compounds↗
PubMedDate not supplied

A fluorometric rapid microassay to identify anti-proliferative compounds for human melanoma cells in vitro.

A simple, rapid and reproducible assay for the determination of melanoma cell proliferation in vitro is described, based on the hydrolysis of a fluorogenic substrate by cell esterases in the cytoplasm of living cells. Human melanoma cells were cultured at several densities in 96-well culture plates for 24 h and were then incubated with 4-methylumbelliferyl heptanoate. The generated fluorescence showed a strong correlation with the cell numbers, similar to those assessed by determining the [3H]thymidine incorporation into cellular DNA and by quantifying the fluorescence obtained after DNA labelling with Hoechst 33258. The latter, however, was less sensitive and exhibited higher standard deviations. In addition, the method reliably detected the anti-proliferative effects of the anti-cancer compounds cisplatin and vindesine. It is, therefore, suggested that the fluorometric assay with 4-methylumbelliferyl heptanoate as substrate could prove useful for the screening of potential anti-cancer agents with anti-proliferative activity.

Antineoplastic Agents↗
PubMedDate not supplied

Anticonvulsant activity of two orally active competitive N-methyl-D-aspartate antagonists, CGP 37849 and CGP 39551, against sound-induced seizures in DBA/2 mice and photically induced myoclonus in Papio papio.

Two novel N-methyl-D-aspartate (NMDA) antagonists, DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid CPG 37849 and the corresponding 1-ethyl ester CGP 39551, were tested as anticonvulsants in DBA/2 mice and photosensitive Senegalese baboons, Papio papio. In DBA/2 mice, CGP 37849 is more potent than CGP 39551 when administered intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) (ED50 for suppression of clonic seizures at 60 min: i.c.v. 0.038 and 0.21 nmol; i.p. 3.40 and 19.1 mumol/kg, respectively). When administered orally in mice, the two compounds are approximately equipotent (ED50 CGP 37849, 35.2 mumol/kg; ED50 CGP 39551, 28.1 mumol/kg). The time course of action of CGP 39551 is exceptionally prolonged: 42 mumol/kg i.p. protects against clonic seizures for 48 h. Protection provided by other NMDA antagonists in mice is of much shorter duration: 2-amino-5-phosphono-pentanoic acid (AP5) 1 h, 2-amino-7-phosphono-heptanoic acid (AP7) 4 h, 2-amino-7-phosphono-heptanoic acid 1-ethyl ester 3 h, 4-(3-phosphonopropyl)-2-piperazine carboxylic acid (CPP) 2 h, cis-4-(phosphonomethyl)-2-piperidine-carboxylic acid (CGS 19755) 4 h, and CGP 37849 4 h. After oral administration of the drugs, the therapeutic index (TI = ratio of the ED50 values for rotorod performance and anticonvulsant protection) remains relatively constant at 5.9-7.2 for 3 h (CGP 37849) and 4.0-6.1 for 24 h (CGP 39551). After i.p. administration, the TI values are CGP 37849 at 1 h 2.4, and at 3 h 20.0, CGP 39551 at 1 h 2.3, at 3 h 7.1, and at 24 h 3.6. In baboons, acute administration of CGP 37849 at doses of 48-191 mumol/kg intravenously (i.v.) suppresses photically induced myoclonus for at least 285 min, with severe side effects at the highest dose tested. CGP 39551 at doses of 169-675 mumol/kg i.v. shows weak anticonvulsant activity only at the highest dose tested (accompanied by severe side effects). CGP 37849 at 48-96 mumol/kg orally (p.o.) fails to protect against photically induced myoclonus up to 4 h after administration, but 191 mumol/kg (40 mg/kg) p.o. produces complete suppression of seizures after 24 h. On the other hand, CGP 39551 at 169 mumol/kg (40 mg/kg) p.o. produces total suppression of seizure activity at 4 h with a longer duration of anticonvulsant action (2-3 days).(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed2004

Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations.

The diterpene salvinorin A from Salvia divinorum has recently been reported to be a high-affinity and selective kappa-opioid receptor agonist (Roth et al., 2002). Salvinorin A and selected derivatives were found to be potent and efficacious agonists in several measures of agonist activity using cloned human kappa-opioid receptors expressed in human embryonic kidney-293 cells. Thus, salvinorin A, salvinorinyl-2-propionate, and salvinorinyl-2-heptanoate were found to be either full (salvinorin A) or partial (2-propionate, 2-heptanoate) agonists for inhibition of forskolin-stimulated cAMP production. Additional studies of agonist potency and efficacy of salvinorin A, performed by cotransfecting either the chimeric G proteins Gaq-i5 or the universal G protein Ga16 and quantification of agonist-evoked intracellular calcium mobilization, affirmed that salvinorin A was a potent and effective kappa-opioid agonist. Results from structure-function studies suggested that the nature of the substituent at the 2-position of salvinorin A was critical for kappa-opioid receptor binding and activation. Because issues of receptor reserve complicate estimates of agonist efficacy and potency, we also examined the agonist actions of salvinorin A by measuring potassium conductance through G protein-gated K(+) channels coexpressed in Xenopus oocytes, a system in which receptor reserve is minimal. Salvinorin A was found to be a full agonist, being significantly more efficacious than (trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide methane-sulfonate hydrate (U50488) or (trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide methane-sulfonate hydrate (U69593) (two standard kappa-opioid agonists) and similar in efficacy to dynorphin A (the naturally occurring peptide ligand for kappa-opioid receptors). Salvinorin A thus represents the first known naturally occurring non-nitrogenous full agonist at kappa-opioid receptors.

Cell Line↗
PubMed1990

Criteria to indicate testosterone administration.

A detection method for testosterone administration was developed using radioimmunoassay to measure the urinary ratios of testosterone (T) to epitestosterone (E) and to luteinizing hormone (LH). A comparative study of the effect on these ratios of a single intramuscular injection of testosterone heptanoate followed by stimulation with human chorionic gonadotrophin (HCG) in three normal men was undertaken. To allow immediate investigation, a commercially supplied epitestosterone antiserum was used. This study showed that both T/E and T/LH ratios could be used to detect testosterone administration, the latter also being an indicator of HCG use due to cross-reactivity with the LH antiserum. Subsequently, an epitestosterone antiserum of superior specificity was raised and used in a study to demonstrate the insignificant effect of exercise on these ratios. Finally, an intramuscular injection of a combined preparation of testosterone/epitestosterone heptanoates resulted in raised ratios of T/LH but not of T/E. This demonstrated the importance of the T/LH ratio in circumstances where the T/E ratio can be easily circumvented.

Adult↗
PubMed1991

Inhibitory effects of prostanoids on the proliferation of transformed human epidermal cells in culture.

The cytotoxic action of various prostanoids was examined on a transformed human epidermal cell line (HSC-1), and methyl(5S,6S,7Z)-5,6-diacetoxy-7-((2S)-4-chloro-2-hydroxy-2-((2 Z+ ++)-2-octenyl)-5-oxo-3-cyclopentenylidene)heptanoate (YM-11), which is a punaglandin compound, was found to be most active. YM-11 exerted a dose-dependent inhibition of HSC-1 cell growth over 0.03 microM (0.01 micrograms/ml), and at 0.3 microM (0.1 micrograms/ml) its growth was completely inhibited. The IC50 value of YM-11 on HSC-1 cell growth was calculated as 0.15 microM (0.05 micrograms/ml). Methyl(E)-7-(5-chloro-2-hydroxy-2-octyl-5-oxo-3-cyclopentenylidene )heptanoate (YM-3), which is also a punaglandin derivative, showed remarkable cytotoxicity on HSC-1 cells with an IC50 of 0.24 microM (0.08 micrograms/ml). Concerning other cytotoxic prostaglandins (PGs), the IC50 values of delta 7-PGA1, delta 12-PGJ2 and PGD2 were 1.5 microM (0.5 micrograms/ml), 2.1 microM (0.75 micrograms/ml) and 5.7 microM (2 micrograms/ml), respectively. On the basis of the present data and previous in vitro and in vivo evidence, punaglandin derivatives may be useful antineoplastic agents for skin cancer.

Cell Division↗
PubMed1993

Androgen-stimulated pubertal growth: the effects of testosterone and dihydrotestosterone on growth hormone and insulin-like growth factor-I in the treatment of short stature and delayed puberty.

The purpose of this study was to investigate the roles of androgenic and estrogenic mechanisms in the stimulation of structural growth and plasma GH in male puberty. To resolve these two possible mechanisms, we compared the effect of two androgens in the treatment of constitutional delay in growth and adolescence: an aromatizable androgen, testosterone (T), and a nonaromatizable androgen, dihydrotestosterone (DHT). Nine adolescent males, Tanner stage 1 or 2, were studied before and during treatment with T enanthate (group A) or DHT heptanoate (group B). After 2.5 months of treatment, the height velocity (HV) was 12.6 +/- 2.8 cm/yr (n = 3) in group A and 8.9 +/- 1.7 cm/yr (n = 6) in group B, both within the range of peak HV for pubertal males. In group A, the integrated concentration of GH (ICGH) increased from 3.12 +/- 0.90 to 13.67 +/- 6.0 micrograms/L (P < 0.05), and plasma insulin-like growth factor-I (IGFI) increased from 126.7 +/- 2.5 to 350.3 +/- 20.3 micrograms/L (P < 0.01); plasma T increased from 0.8 +/- 0.5 to 33.8 +/- 11.0 nmol/L (P < 0.001), and the LH response to LHRH decreased from 27.6 +/- 10.7 to 5.9 +/- 2.5 IU/L (P = NS). In group B, ICGH decreased from 4.32 +/- 0.61 to 2.39 +/- 0.42 (P < 0.025), and IGF-I decreased from 218.3 +/- 39.2 to 184.0 +/- 15.8 (P = NS). Plasma T increased from 2.0 +/- 0.5 to 2.7 +/- 0.8 (P = NS), and the LH response to LHRH decreased from 45.7 +/- 14.5 to 10.7 +/- 5.8 (P < 0.05). To further evaluate the mechanism of the effect of DHT on plasma GH, seven male subjects with adolescent gynecomastia were treated with DHT heptanoate, and their responses were studied at 1 week and 3.5 months. ICGH decreased in conjunction with a decrease in the integrated T concentration (r = -0.77; P < 0.001) and to a slight degree with decreasing plasma estradiol (r = -0.39; P < 0.2). Plasma IGF-I did not show a significant change in the subjects with gynecomastia. Thus, the increase in GH at puberty in males appears to be due to an estrogen-dependent mechanism. The suppressive effect of DHT on GH secretion may be due to either suppression of estradiol production or a direct effect. Acceleration of HV into the peak pubertal range by DHT without an increase in plasma GH suggests that an increase in GH is not necessary for the pubertal growth spurt.

Adolescent↗
PubMed2004

[Studies on synthesis of polyhydroxyalkanoate consisting of 3-hydroxyvalerate by Aeromonas hydrophila].

Polyhydroxyalkanoates (PHA) is a family of microbially synthesized polyesters consisting of various 3-hydroxyalkanoate monomers. Aeromonas hydrophila 4AK4 could be able to synthesize PHA copolymer consisting of 3-hydroxybutyrate (3-HB) and 3-hydroxyhexanoate (3-HHx). No data has been reported about the ability to synthesize the PHA with other monomers in A. hydrophila. In this study, propionic acid, valeric acid, heptanoic acid, nonanoic acid and undecanoic acid were used together with gluconate to find out whether A. hydrophila 4AK4 could synthesize the PHA consisting of odd carbon atom number monomers. The result showed that A. hydrophila 4AK4 could not growth when supplied with propionic acid, valeric acid, heptanoic acid and nonanoic acid and only undecanoic acid could be used to synthesize PHA. Wild type and recombinant A. hydrophila 4AK4 harboring phaA (beta-ketothiolase) and phaB (acetoacetyl-CoA reductase) were cultivated with undecanoic acid and glucose or undecanoic acid and gluconate served as carbon sources. PHA consisting of 3-HB and 3-hydroxyvalerate (3-HV) could be produced by both wild type and recombinant A. hydrophila 4AK4 and the latter could produce PHA with more 3-HB monomer. When the ratio of glucose or gluconate to undecanoic acid was 1:1, the cell dry weight (CDW) of A. hydrophila 4AK4 reached 1.14 g/L and PHA content was 60% of the CDW after cultivation for 24 h. When lauric acid and undecanoic acid were served as co-substrate, A. hydrophila 4AK4 could produce copolyester consisting of 3-HB, 3-HV and 3-HHx. Along with the increase of undecanoic acid proportion in the mixed carbon source, the 3-HV content of copolymer was increased while the 3-HB and 3-HHx content were decreased. In all cases, the CDW decreased along with the increase of undecanoic acid concentration, which indicated that undecanoic acid was not very good for A. hydrophila 4AK4 growth.

Aeromonas hydrophila↗
PubMed1976

Inhibition of adenosine 3':k'-monophosphate accumulation white fat acids, lactate, and beta-hydroxybutyrate.

The large increase in cyclic AMP accumulation by rat white fat cells seen in the presence of lipolytic agents plus methylxanthines and adenosine deaminase was markedly inhibited by lactate. However, lipolysis was unaffected by lactate. Octanoate, hexanoate, heptanoate, and beta-hydroxybutyrate inhibited both cyclic AMP accumulation and lipolysis by rat fat cells. The mechanism by which these acids inhibit lipolysis differs from that for long chain fatty acids such as oleate. Oleate directly inhibited triglyceride lipase activity of homogenized rat adipose tissue. In contrast, octanoate, beta-hydroxybutyrate, and lacatate had no effect on triglyceride lipase activity. Hormone-stimulated adenylate cyclase activity of rat fat cell ghosts was inhibited by oleate and 4mM octanoate but not by 1.6 mM octanoate, heptanoate, hexanoate, beta-hydroxybutyrate or lactate. None of the acids affected the soluble protein kinase activity of rat adipose tissue. There was no stimulation by lactate, butyrate, beta-hydroxybutyrate, or octanoate of the soluble or particulate cyclic AMP antilipolytic action of a short chain acid such as octanoate or hexanoate was not accompanied by any drop in total fat cell ATP. The mechanism by which lactate lowers cyclic AMP but not lipolysis remains to be established.

Adenylyl Cyclases↗
PubMed1980

[Synthesis of compounds with antisecretory activity].

Some indole and pyrrolidone derivatives of two peptides, H-Ile-His-Pro-NH2 and N epsilon-Boc-Lys-Ile-His-Pro-NH2, were prepared and tested for antisecretory activity. A report is given of the synthetic scheme used for the two peptides which is a modified Jones procedure, the preparation of pyrrolidin-5-one-N-heptanoic acid and 1H-indol-3-heptanoic acid, the introduction on the peptide chain of indole and pyrrolidone radicals and the results of the pharmacological investigation.

Animals↗
PubMed2000

Enhancement of mass transfer using colloidal liquid aphrons: measurement of mass transfer coefficients in liquid-liquid extraction.

Interphase mass transfer of a sparingly soluble solute is often the rate-limiting step in multiphase biocatalytic processes. Colloidal liquid aphrons (CLA) provide very large interfacial areas, and thus could enhance mass transfer in such processes. The aim of this study was to characterize mass transfer properties of CLA dispersions during transfer of heptanoic acid from water to limonene. The interfacial area per unit volume (a), film mass transfer coefficient (K(L)), and volumetric mass transfer coefficient (K(L)a) values were determined in a stirred-tank reactor. These results were used, along with a literature correlation, to estimate the mass transfer coefficient of the surfactant-stabilized shell surrounding the CLA. The very large increase in a provided by the CLA was only partially offset by a slight increase in the mass transfer resistance of the shell. As a result, the range of K(L)a values obtained using CLA was about an order of magnitude greater than that obtained using a conventional dispersion. The concentration of the aqueous-phase surfactant used to form the CLA strongly affected the Sauter mean diameter of the CLA; however, the concentration of the nonpolar-phase surfactant had little effect. These results suggest that CLA have considerable potential for multiphase biocatalytic applications.

Biotechnology↗
PubMedDate not supplied

Response of Nitella internodal cell to chemical stimulation. A model for olfactory receptor system.

Electrical response to excitable internodal cell of Nitella was studied by applying various kinds of odorants to the cell. Changes in membrane potential and resistance during responses induced by odorants were measured intracellularly under a variety of ionic environments in the media. Results were: 1) Some odorants (coumarin, isoamylacetate, methylacetate, 1-octanol, 1-butanol, 1-propanol) produced an all-or-nothing type action potential when the concentration of odorant exceeded a certain threshold. The action potential was followed by a gradual depolarization of the potential whose amplitude depended on the odorant concentration, C. Other odorants (heptanoic acid, beta-ionon) induced gradual depolarization of the membrane potential without evoking an action potential. 2) Membrane resistance Rm changed in various ways during depolarization: some odorants led to a temporal or gradual decrease in Rm, and others caused an increase in Rm when the membrane potential was depolarized by the application of odorants. 3) Magnitude of response to odorants OR was found to be represented by the following equation: OR =(alpha + beta square root I) log (C/Cth) for C greater than or equal to Cth where alpha and beta are constants for a given odorant, I the ionic strength in the medium, and Cth the threshold concentration of the odorant. 4) Plots of olfactory threshold of human and of internodal cell of Nitella gave a straight line having slope unity. 5) Local application of odorants on the internodal cell induced impulses which transmitted from the part treated by odorants to the other portion. Physico-chemical and physiological implications of the results obtained were discussed.

1-Propanol↗
PubMed2004

Chemosensory additivity in trigeminal chemoreception as reflected by detection of mixtures.

A series of experiments probed into the degree of chemosensory detection additivity exhibited by mixtures of ethyl propanoate and heptanoate in terms of their trigeminal detectability via nasal pungency (i.e., irritation) and eye irritation. Nasal pungency was tested in subjects lacking a functional sense of smell (i.e., anosmics) to avoid olfactory biases. First, we built concentration-detection functions for each chemical and sensory endpoint. Second, we used the data from the functions to prepare mixtures of the two compounds in complementary proportions, and suitable single-chemical standards, all of which should be equally detectable under a rule of complete additivity, i.e., independence of detection. Third, we compared the experimentally obtained detectability with that expected under such rule. The outcome revealed that, at a low detectability level (but still above chance), the mixtures showed complete additivity for both trigeminal endpoints. At a high detectability level (but below perfect detection), the mixtures showed complete additivity for nasal pungency but less than complete additivity for eye irritation. In the context of previous studies, the results consolidate a picture of higher degree of detection additivity at perithreshold levels in trigeminal than in olfactory chemoreception. The outcome presents another line of evidence suggesting broader chemical tuning in chemesthesis compared to olfaction.

Adult↗
PubMed2006

Abiotic condensation synthesis of glyceride lipids and wax esters under simulated hydrothermal conditions.

Precursor compounds for abiotic proto cellular membranes are necessary for the origin of life. Amphipathic compounds such as fatty acids and acyl glycerols are important candidates for micelle/bilayer/vesicle formation. Two sets of experiments were conducted to study dehydration reactions of model lipid precursors in aqueous media to form acyl polyols and wax esters, and to evaluate the stability and reactions of the products at elevated temperatures. In the first set, mixtures of n-nonadecanoic acid and ethylene glycol in water, with and without oxalic acid, were heated at discrete temperatures from 150 ( composite function)C to 300 ( composite function)C for 72 h. The products were typically alkyl alkanoates, ethylene glycolyl alkanoates, ethylene glycolyl bis-alkanoates and alkanols. The condensation products had maximum yields between 150 ( composite function)C and 250 ( composite function)C, and were detectable and thus stable under hydrothermal conditions to temperatures < 300 ( composite function)C. In the second set of experiments, mixtures of n-heptanoic acid and glycerol were heated using the same experimental conditions, with and without oxalic acid, between 100 ( composite function)C and 250 ( composite function)C. The main condensation products were two isomers each of monoacylglycerols and diacylglycerols at all temperatures, as well as minor amounts of the fatty acid anhydride and methyl ester. The yield of glyceryl monoheptanoates generally increased with increasing temperature and glyceryl diheptanoates decreased noticeably with increasing temperature. The results indicate that condensation reactions and abiotic synthesis of organic lipid compounds under hydrothermal conditions occur easily, provided precursor concentrations are sufficiently high.

Esters↗
PubMed1989

The inhibition of cytoplasmic acetoacetyl-CoA thiolase by a triyne carbonate (L-660, 631).

The compound L-660, 631 (2-oxo-5-(1-hydroxy-2,4,6-heptatriynyl)-1,3-dioxolane-4 heptanoic acid), a natural product isolated from an Actinomycete culture, was found to inhibit rat liver cytosolic acetoacetyl-CoA thiolase, the first step in the cholesterol biosynthesis pathway, with an IC50 of 1.0 x 10(-8) M. The inhibitor had no effect on other sulfhydryl containing enzymes of lipid synthesis such as HMG-CoA synthase, HMG-CoA reductase, and fatty acid synthase. When tested in cultured human liver Hep G2 cells the compound inhibited the incorporation of 14C-acetate and 14C-octanoate into sterols 56% and 48% respectively at 3 x 10(-6) M with no effect on fatty acid synthesis. No noticeable effect was seen on fatty acid biosynthesis. This strongly suggests that the locus of inhibition of acetate incorporation into sterols found with this compound is the acetoacetyl-CoA thiolase step in the cholesterol biosynthesis pathway.

Acetyl-CoA C-Acetyltransferase↗
PubMed1993

Conventional and enantioselective determination of a new blood glucose-lowering agent in biological fluids using liquid-liquid extraction and high-performance liquid chromatography.

Two analytical methods are described for the determination of 2-(4-tert.-butylphenoxy)-7-(4-chlorophenyl)heptanoic acid sodium salt (I) in animal models (beagle dog and rat). Method 1 is conventional reversed-phase high-performance liquid chromatography on an octadecylsilane column with an eluent of acetonitrile-0.02 M potassium buffer (pH 3) (65:35, v/v). Method 2 is used for the enantioselective determination of I. This method uses a chiral column (Chiralcel OJ) with an eluent of n-hexane-2-propanol (95:5, v/v) containing 3 ml/l trifluoracetic acid. The analytical procedure has a recovery of more than 90%; within-run precision of less than 5.1%, and between-run precision of less than 4.3%.

Animals↗