Cis Counterparts Research Articles

Cellular pharmacology of cis and trans pairs of platinum complexes in cisplatin-sensitive and -resistant human ovarian carcinoma cells

The cellular pharmacology of two pairs of cis and trans platinum complexes has been studied in three human ovarian carcinoma cell lines, a parental relatively cisplatin-sensitive line (CH1), a subline possessing acquired cisplatin resistance (3-fold; CH1cisR) and an intrinsically cisplatin resistant line (13-fold; SKOV-3). Growth inhibition studies showed that both JM335 [ trans ammine (cyclohexylaminedichloro dihydroxo) platinum(IV)] and its platinum(II) dichloro homolog JM334 were relatively less cross-resistant against both acquired and intrinsic cisplatin resistant cells. In contrast, resistance circumvention was not apparent in these cell lines with their cis isomeric counterparts (JM149 for JM335 and JM118 for JM334). The trans compound JM335 was more potent than its cis isomer against all three cell lines. There was no clear correlation between intracellular accumulation following 2 h exposure to each compound and resulting DNA platination or growth inhibition. The selective activity of the trans platinum complexes against the SKOV-3 cell line correlated with a deficiency in the repair of adducts within a fragment of the N- ras gene induced by trans compounds whereas adducts induced by the cis counterparts, and cisplatin, were repaired. The CH1 parental line appeared repair deficient at the gene-specific level to adducts induced by both cis ( including cisplatin) and trans compounds. Resistance in CH1cisR was associated with a lack of gene-specific repair of lesions formed by JM118 and JM149. All four compounds induced apoptosis in all three cell lines, as measured by fluorescent microscopy and field inverted gel electrophoresis, although the kinetics of apoptosis was markedly faster for the trans versus cis compounds. In summary, the trans platinum complexes JM335 and JM334 possess unique cellular properties compared to their cis counterparts particularly with respect to gene specific repair of DNA adducts and the rate of induction of apoptosis.

A method to detect nonprolinecis peptide bonds in proteins

Based on the geometrical parameters around seventeen incorrectly assigned trans conformations of peptide bonds in protein structures and their correct cis counterparts, we have devised an algorithm that is capable of detecting these sites. The algorithm was optimized to reliably find all of the seventeen test cases. It can be used to quickly scan an atomic coordinate file or the complete Brookhaven Protein Data Base for more likely candidates for non-Pro cis peptide bonds. Also, it can be of help to guide the crystallographer in intermediate stages of structure determination towards suspect areas.

In vitro hydrolysis of polyunsaturated fatty acid N-acyloxymethyl derivatives of theophylline

A series of fatty acid N-acyloxymethyl derivatives of theophylline was prepared to determine the effects of varying the nature of the fatty acid on their in vitro rates of hydrolysis using porcine liver esterase and human plasma. The carboxylic acids examined include acetic (Ac), valeric (VA), nonanoic (NA), stearic (SA), oleic (OA), linoleic (LA), γ-linolenic (GLA), α-linolenic (ALA), eicosapentaenoic (EPA), elaidic (EA) and linoelaidic acid (LEA). When exposed to porcine liver esterase the NA acid derivative was hydrolyzed about 80 times faster than the triple bond GLA and ALA derivatives, which were hydrolyzed about four times as fast as the double bond LA derivative, which was hydrolyzed three times as fast as the single bond OA derivative. In human plasma the VA acid derivative was hydrolyzed over 100 times faster than the GLA derivative. Both the trans fatty acid EA and LEA derivatives were hydrolyzed slower than their cis counterparts. In both porcine esterase and human plasma, the derivatives displayed the classical parabolic relationship when the logarithm of the rate constant, k, was plotted versus the lipophilicity index, log K. Although the unsaturated fatty acid derivatives with three or more double bonds are not hydrolyzed at the maximum rate, they are hydrolyzed at markedly faster rates than the corresponding saturated or mono-unsaturated derivatives and as such still may serve as a delivery vehicle for other drugs.

Trans fatty acids and cardiovascular risk

The major source of trans unsaturated fatty acid bearing fats ( trans fats) is the partially hydrogenated fats present in margarines, salad and cooking oils. When ingested, trans fats are deposited in tissues but disappear when the nutritional stimulus is removed. They have no adverse effects on growth or reproduction in rats. Trans fats are hypercholesterolemic for rabbits and monkeys but no more atherogenic than their cis counterparts. In man, trans fats elevate cholesterol but the extent of elevation may depend on the level of dietary linoleic acid. In some, but not all, studies they elevate Lp(a); the difference may reflect the presence of specific trans isomers — an area that merits further studies. Tissue of subjects with coronary disease contain no more trans fatty acids than those of controls. Reviews of the literature by expert committees in the US and UK conclude that at current levels of intake dietary trans fats pose no health problems. However, more research is needed especially with regard to pregnancy, lactation, and neonatal health. Current concerns should not deflect our attention from the larger aspects of fat and health.

Chemistry and Stereochemistry of Benzyl-Benzyl Interactions in MH+ Ions of Dibenzyl Esters upon Chemical Ionization and Collision-induced Dissociation Conditions

Isobutane chemical ionization mass spectra of dibenzyl esters of a wide variety of aliphatic, olefinic, alicyclic and aromatic dicarboxylic acids exhibit abundant m/z 181 C 14 H + 13 ions, indicating a highly general rearrangement process involving the formation of a new bond between the two benzyl groups. An extensive collision-induced dissociation and deuterium labeling study suggested that these ions are an almost equimolar mixture of isomeric α-o-tolylbenzyl, α-p-tolylhenzyJ and p-benzylbenzyl cation structures, and this composition is identical for all the diesters examined. This structural assignment of the C 14 H 13 + ions suggests a mechanistic pathway for their generation, based on the formation of the new bond between the benzyl methylene group of the protonated benzoxycarb-onyl and the phenyl ring of the other ester moiety via π- (and/or ion-neutral) and α-complexe. Stereoisomeric diesters show an unusual steric effect: trans-isomers give rise to much more abundant C 14 H + 13 ions than the cis counterparts. This behavior is explained by stabilized proton-bridged structures of the MH+ ions of the cis-isomers.

Trans-2-Cyanocycloalkanols: Versatile Synthons for Alicycliccis- andtrans-1,3-Amino Alcohols

From trans-2-hydroxycyclopentanecarbonitrile (1) and trans-2-hydroxycyclohexanecarbonitrile (2), a number of trans-2-aminomethylcycloalkanols are prepared by reductive alkylation. Inversion of trans-N-acylaminocycloalkanols by treatment with thionyl chloride and subsequent hydrolysis gives the cis counterparts. Enantiomerically pure trans-2-aminomethylcyclohexanols are also prepared

Neat and admixed mesomorphic polysiloxane stationary phases for open-tubular column gas chromatography

A mesomorphic polysiloxane (MEPSIL) solvent, employed either neat or in admixture with SE-30 poly(dimethylsiloxane) (PDMS) diluent, is shown to be a highly selective stationary phase for open-tubular column gas-liquid chromatography. Mixtures of cis and trans fatty acid methyl esters (FAME) are resolved isothermally in under 10 min with neat nematic MEPSIL phase, where trans isomers are retained longer than their cis counterparts. Programmed-temperature separations of more complex mixtures of FAME solutes also demonstrate that elution order is by increasing carbon number and that within a group of the same carbon number, retentions increase with increasing saturation, which is completely opposite to the order of selectivity given by conventional phases. Shape selectivity of the nematic MEPSIL phase is further illustrated by the separation of samples containing polychlorinated biphenyl (PCB) solutes, where inter alla congener 198 elutes well before 128. Blending the MEPSIL solvent with SE-30 is then shown not to depress significantly the nematic/isotropic transition of the pure mesomorph, and blends of up to 3:1 SE-30/MEPSIL are virtually as selective as neat MEPSIL at temperatures in excess of 300/sup 0/C. However, the crystal/nematic transition cannot thereby be lowered substantially, nor can the lower limiting chromatographic efficiency be improved to much beyondmore » that of the neat phase. Even so, blended-phase columns exhibit in excess of 3200 N m/sup -1/ at elevated temperatures, which is sufficient to provide good resolution, isothermally, of 8 of 10 methylbenz(a)anthracene isomers at 240/sup 0/C, and of 9 of 10 methylbenzo(a)pyrene solutes at 275/sup 0/C.« less

Cis-Trimedlure: Attraction for the Mediterranean Fruit Fly (Diptera: Tephritidae) and Isomeric Structural Assignments1

trans -Trimedlure, 1,1-dimethylethyl 4(and 5)-chloro- trans -2-methylcyclohexane-1-carboxylate (TML), is a mixture of four isomers and is the survey and detection lure for the Mediterranean fruit fly, Ceratitis capitata (Wiedemann). It is significantly more attractive than cis -TML, 1,1-dimethylethyl 4(and 5)-chloro- cis -2-methylcyclohexane-1-carboxylate, which is also a mixture of four isomers. Relatively large quantities of cis -TML can be added to trans -TML without affecting attraction, thus, commercial TML, which normally contains 5–10% cis -TML, is as attractive as pure trans -TML. This finding is important in establishing quality control standards for TML used in survey and detection programs. By use of epimerization reactions, the four trans -isomers, whose structures are known, were converted to their cis counterparts. The structural identification of each cis isomer was, thus, established.

Occurrence of some mono- cis-isomers of asymmetric C 40-carotenoids

The 9- cis-isomers of antheraxanthin [(3 S,5 R,6 S)-5,6-epoxy-5,6- dihydro-β, β-carotene-3,3′-diol] and lutein epoxide [(3 S,5 R,6 S, 3′ R,6′ R)-5,6-epoxy-5,6-dihydro-β, ε-carotene-3,3′-diol] were found to occur without their 9′- cis counterparts in the non-photosynthetic tissues of several higher plants. 9- cis-lutein [(3 R,3′ R,6′ R)- β,ε-carotene-3,3′-diol], on the other hand, was observed together with its 9′- cis counterpart in the samples investigated. The qualitative distribution of carotenoids is also reported.

Purification and properties of pyrethroid carboxyesterase in rat liver microsome

Pyrethroid carboxyesterase which hydrolyzes the esters of chrysanthemumic acid was purified from rat liver microsome by cholic acid solubilization, ammonium sulfate fractionation, heat treatment, and DEAE-Sephadex A-50 column chromatography. The 45-fold purified enzyme (38% yield) is likely to consist of single protein, as evidenced by polyacrylamide gel disc electrophoresis and Sephadex G-100 column chromatography, and had a molecular weight of approximately 74,000 and a K m of 0.21 m M. It is susceptible to inhibition by organophosphates and carbamate insecticides and insensitive to pCMB, mercuric ion, and cupric ion. It is capable of hydrolyzing trans isomers of synthetic pyrethroids much more rapidly (five to ten times) than the cis counterparts. The purified pyrethroid carboxyesterase is apparently identical in nature with malathion carboxyesterase and with p-nitrophenyl acetate carboxyesterase.

Identification of Natural and Synthetic Polyisoprene Vulcanizates by Thermal Analysis

Abstract 1. NR and IR vulcanizates can be distinguished from one another by their DSC and DTG curves. 2. Thermal curves remain more or less unaffected by recipe changes. 3. Identification of blends of NR and IR is complicated since different IR's have different exotherm areas. 4. Natural and synthetic trans-polyisoprenes can be distinguished from one another, as well as from their cis counterparts, by their DSC and DTG curves. 5. Differences observed in the natural and synthetic polyisoprenes seem to be due to a higher amount of cyclized product, formed as a result of catalysis by the residual inorganic material in the synthetic product.