On the specificity of the folin and lowry reagents for amine derivatives.

Reactivities of several amine derivatives with the Folin and Lowry reagents were examined. Tertiary amines reacted with the Folin reagent to produce a blue color, and secondary amines having a 2-hydroxyethyl group reacted with the Folin reagent only in the presence of Cu²⁺, i.e., with the Lowry reagent. On the other hand, primary and quarternary amines and amine N-oxides produced no color with either reagent. Reactivities of tertiary amines were greatly influenced by the nature of the N-substituted groups, and the color yield of those forming stable chelate complexes with metals was strongly inhibited by the presence of Cu²⁺, indicating that the formation of a stable complex with Cu²⁺ reduces the reactivity of tertiary amino nitrogen. The requirement of Cu²⁺ for the color development with secondary amines having a 2-hydroxyethyl group may be due to the formation of weak chelate complex with Cu²⁺.     

Lactones 34 [1]. Application of alcohol dehydrogenase from horse liver (HLADH) in enantioselective synthesis of δ- and ɛ-lactones

The ability of horse liver alcohol dehydrogenase (HLADH) to the enantioselective oxidation of primary–primary, primary–secondary and primary-tertiary aliphatic 1,5- and 1,6-diols 1a–i was studied. No enantioselectivity of the transformations of primary–primary 1,6-diols 1a–d to ɛ-lactones 4a–d was observed. Regioselective oxidation of primary–secondary 1,6-diols 1e,f and 1,5-diols 1h,i afforded enantiomerically enriched ɛ-lactones 4e,f and δ-lactones 4h,i. ɛ-Lactones 4e,f were formed with higher enantiomeric excesses (e.e. = 85–99%). Enzymatic oxidation of primary–tertiary 1,6-diol 1g did not give lactone product.     

Synthesis and study of new paramagnetic and diamagnetic verapamil derivatives

New derivatives of verapamil (1) modified with nitroxides and their precursors were synthesized and screened for reactive oxygen species (ROS)-scavenging activities. The basic structure was modified by changing the nitrile group to an amide or the methyl substituent on tertiary nitrogen with nitroxides and their reduced forms (hydroxylamine and secondary amines). Among the new verapamil derivatives compound 16B [Mohan, I. K.; Kahn, M.; Wisel, S.; Selvendiran, K.; Sridhar, A.; Carnes, C.A.; Bognár, B.; Kálai, T.; Hideg, K.; Kuppusamy, P. Am. J. Physiol. Heart Circ. Physiol. 2009, 296, 140], modified with hydroxylamine salt of 2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridine-1-yloxyl proved to be the best ROS scavenger in vitro and protected HSMC and CHO cells against H₂O₂ induced damage.     

Quantitative description of the process of architecture formation inViburnum dilatatum andV. wrightii (Caprifoliaceae)

Process of architecture formation was comparatively analyzed usingViburnum dilatatum andV. wrightii (Caprifoliaceae). In both species, orthotropic primary axes emerge from the basal parts of mother plants near the ground level. The primary axes grow vigorously in the first and the subsequent few years of their development. Later on, they decrease their elongation rates gradually and many axillary buds stay in dormancy. A few of the axillary buds emerge after several years' dormancy and elongate vigorously forming orthotropic secondary axes. inViburnum dilatatum, nearly 50% of the primary axes develop the secondary axes. The secondary axes elongate as vigorous as the primary axes. Furthermore, more than 20% of the secondary axes form the tertiary axes, and only 10% of the tertiary axes form the quarternary axes. In contrast, inViburnum wrightii only less than 25% of the primary axes form the secondary axes, and there is no tertiary or quarternary axis. The secondary axes of this species elongate less vigorously than the primary axes. As the result of those differences in the axis formation,Viburnum wrightii forms a simpler architecture thanV. dilatatum.     

A Modified Regeneration Method for Streptomycete Protoplasts

The racemization of optically active imidazoline derivatives catalyzed by amines and alcohols was investigated. The racemization was effected by the catalysis of primary and secondary amines, but not by tertiary amines. In t-BuOH, imidazolines were racemized much more slowly than in primary alcohols. The mechanism through a pseudo-six-membered cyclic transition state was proposed for the racemization.     

Synthesis and biological evaluation of novel alkyl amide functionalized trifluoromethyl substituted pyrazolo[3,4-b]pyridine derivatives as potential anticancer agents

A series of novel alkyl amide functionalized trifluoromethyl substituted pyrazolo[3,4-b]pyridine derivatives 5, 6 and 7 were prepared starting from 6-phenyl-4-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-3-amine 3 via selective N-alkylation, followed by reaction with different primary aliphatic amines, cyclic secondary amines or l-amino acids under different set of conditions. All the synthesized compounds 5, 6 and 7 were screened for anticancer activity against four cancer cell lines such as A549—Lung cancer (CCL-185), MCF7—Breast cancer (HTB-22), DU145—Prostate cancer (HTB-81) and HeLa—Cervical cancer (CCL-2). The compounds 5i and 6e are found to have promising bioactivity at micro molar concentration.     

Structure and chemical composition of endodermal and rhizodermal/hypodermal walls of several species

CWM, isolated cell wall material
ECW, isolated endodermal cell walls
G, guaiacyl monomer
H, p-hydroxyphenyl monomer
HCW, isolated hypodermal cell walls
RHCW, isolated rhizodermal and hypodermal cell walls
S, syringyl monomer
XV, isolated xylem vessels

Endodermal cell walls of the three dicotyledoneous species Pisum sativum L., Cicer arietinum L. and Ricinus communis L. were isolated enzymatically and analysed for the occurrence of the biopolymers lignin and suberin. From P. sativum, endodermal cell walls in their primary state of development (Casparian strips) were isolated. Related to the dry weight, these isolates contained equal amounts of suberin (2·5%) and lignin (2·7%). In contrast, the endodermal cell walls of C. arietinum and R. communis, which were nearly exclusively in their secondary state of development, contained significantly higher proportions of suberin (10–20%) and only traces of lignin (1–2%). The results of the chemical analyses were supported by a microscopic investigation of Sudan III-stained root cross-sections, showing a Casparian strip restricted to the radial walls of the endodermis of P. sativum and well-pronounced red suberin lamellae in C. arietinum and R. communis roots. Compared with recently investigated monocotyledoneous species, higher amounts of suberin by one order of magnitude were detected with the secondary state of development of dicotyledoneous species. Furthermore, the carbohydrate and protein contents of primary (Clivia miniata Reg. and Monstera deliciosa Liebm.), secondary (C. arietinum and R. communis) and tertiary endodermal cell walls (Allium cepa L. and Iris germanica L.) were determined. The relative carbohydrate content of secondary endodermal cell walls was low (14–20%) compared with the content of primary (42–50%) and tertiary endodermal cell walls (60%), whereas the protein content of isolated endodermal cell walls was high in primary (13%) and secondary (8%) and low in tertiary endodermal cell walls (0·9–2%). The results presented here indicate that the quantitative chemical composition of primary, secondary, and tertiary endodermal cell walls varies significantly. Finally, cell wall proteins are described as an additional important constituent of endodermal cell walls, with the highest concentrations occurring in primary (Casparian strips) and secondary endodermal cell walls.     

Antileukemic activity of aminoparthenolide analogs

A series of aminoparthenolide analogs have been synthesized through a diastereoselective conjugate addition of several primary and secondary amines to the α-methylene-γ-butyrolactone function of the very lipophilic sesquiterpene lactone, parthenolide. Seventeen of the above amines derivatives were evaluated in a full panel of 60 cancer cell lines for anticancer activity. Compound 12, derived from tyramine, was found to be cytostatic as well as cytotoxic toward acute lymphoblastic leukemia cells (ALL, CCRF-CEM) at nanomolar concentrations, while the (R)-(1,2,3,4-tetrahydro-1-naphthyl)amino derivative 9 was found to be cytostatic toward human anaplastic large T-cell lymphoma (SR) cells at concentrations below 10 nM.     

Polymerization of N-carboxyanhydrides of various α-amino acids using secondary amines as initiator

In the polymerizations of alanine, γ-ethyl glutamate, and leucine N-carboxyanhydrides (NCA's) initiated by tertiary amines and some secondary amines such as N-methyl-L -alanine dialkylamide, a stereoselectivity was observed: the polymerization rates of L - and D -NCA's were identical to each other and larger than that of DL -NCA. However, this selectivity was not observed in the polymerizations of valine and isoleucine NCA's initiated by N-methyl-L -alanine dialkylamide. The stereoselective polymerizations of valine and isoleucine NCA's were induced only with tetriary amines such as tri-n-butylamine. N-Methyl-L -alanine di-alkylamide has been shown to initiate the polymerization of usual α-amino acid NCA according to the activated-NCA mechanism, but it initiated the polymerizations of valine and isoleucine NCA's according to the primary amine-type mechanism. This is because in the latter NCA's the N–H group is masked by the adjacent C^β-branched alkyl substituent against the approach of the secondary amine. Poly(DL -alanine)s produced in the stereoselective polymerization had higher viscosities and were more stereoblock-like than those produced without the stereoselectivity. These experimental results indicate that the stereoselective polymerization is possible only when the polymerization proceeds through the activated-NCA mechanism.     

Comparative investigation of primary and tertiary endodermal cell walls isolated from the roots of five monocotyledoneous species: chemical composition in relation to fine structure

The chemical composition of isolated endodermal cell walls from the roots of the five monocotyledoneous species Monstera deliciosa Liebm., Iris germanica L., Allium cepa L., Aspidistra elatior Bl. and Agapanthus africanus (L.) Hoffmgg. was determined. Endodermal cell walls isolated from aerial roots of M. deliciosa were in their primary developmental state (Casparian bands). They contained large amounts of lignin (6.5% w/w) and only traces of suberin (0.5% w/w). Endodermal cell walls isolated from the other four species were in their tertiary developmental state. Lignin was still the more abundant cell wall polymer with amounts ranging from 3.8% (w/w, A. cepa) to 4.5% (w/w, I. germanica). However, compared to endodermal cell walls in their primary state of development (Casparian bands), tertiary endodermal cell walls contained significantly higher amounts of suberin, ranging from 1.8% (w/w, I. germanica) to 3.0% (w/w, A. africanus). Thus, chemical characterization of endodermal cell walls from five different species revealed that lignin was the dominant cell wall polymer in the Casparian band of M. deliciosa, whereas tertiary endodermal cell walls contained, in addition to lignin, increasing amounts of suberin (I. germanica, A. cepa, A. elatior and A. africanus). Besides the two biopolymers lignin and suberin, cell wall carbohydrates in the range of between 40 and 60% were also quantified. The sum of all cell wall compounds investigated by gas chromatography resulted in a recovery of 50–80% of the dry weight of the isolated cell wall material. Quantitative chromatographic results in combination with microscopic studies are consistent with the existence of a distinct suberin lamella and lignified tertiary wall deposits. From these data it can be concluded that the barrier properties of the endodermis towards the apoplastic transport of ions and water will increase from primary to tertiary endodermal cell walls due to their increasing amounts of suberin. Received: 23 August 1997 / Accepted: 28 January 1998     

Grafting of antibacterial polymers on stainless steel via surface‐initiated atom transfer radical polymerization for inhibiting biocorrosion by Desulfovibrio desulfuricans

To enhance the biocorrosion resistance of stainless steel (SS) and to impart its surface with bactericidal function for inhibiting bacterial adhesion and biofilm formation, well‐defined functional polymer brushes were grafted via surface‐initiated atom transfer radical polymerization (ATRP) from SS substrates. The trichlorosilane coupling agent, containing the alkyl halide ATRP initiator, was first immobilized on the hydroxylated SS (SS‐OH) substrates for surface‐initiated ATRP of (2‐dimethylamino)ethyl methacrylate (DMAEMA). The tertiary amino groups of covalently immobilized DMAEMA polymer or P(DMAEMA), brushes on the SS substrates were quaternized with benzyl halide to produce the biocidal functionality. Alternatively, covalent coupling of viologen moieties to the tertiary amino groups of P(DMAEMA) brushes on the SS surface resulted in an increase in surface concentration of quaternary ammonium groups, accompanied by substantially enhanced antibacterial and anticorrosion capabilities against Desulfovibrio desulfuricans in anaerobic seawater, as revealed by antibacterial assay and electrochemical studies. With the inherent advantages of high corrosion resistance of SS, and the good antibacterial and anticorrosion capabilities of the viologen‐quaternized P(DMAEMA) brushes, the functionalized SS is potentially useful in harsh seawater environments and for desalination plants. Biotechnol. Bioeng. 2009;103: 268–281. © 2009 Wiley Periodicals, Inc.     

Synthesis and characterization of a triazine dendrimer that sequesters iron(III) using 12 desferrioxamine B groups

The synthesis of a third generation triazine dendrimer, 1, containing multiple, iron-sequestering desferrioxamine B (DFO) groups is described. Benzoylation of the hydroxamic acid groups of DFO and formation of a reactive dichlorotriazine provide the intermediate for reaction with the second generation dendrimer displaying twelve amines. This strategy further generalizes the ‘functional monomer’ approach to generate biologically active triazine dendrimers. Dendrimer 1 is prepared in seven steps in 35% overall yield and displays 12 DFO groups making it 56% drug by weight. Spectrophotometric titrations (UV–vis) show that 1 sequesters iron(III) atoms with neither cooperativity nor significant interference from the dendrimer backbone. Evidence from NMR spectroscopy and mass spectrometry reveals a limitation to this functional monomer approach: trace amounts of O-to-N acyl migration from the protected hydroxamic acids to the amine-terminated dendrimer occurs during the coupling step leading to N-benzoylated dendrimers displaying fewer than 12 DFO groups.     

Synthesis,GluN2B affinity and selectivity of benzo[7]annulen-7-amines

Due to their beneficial side effect profile, NMDA receptor antagonists interacting selectively with the allosteric ifenprodil binding site of the GluN2B subunit are of major interest for the treatment of neurological and neurodegenerative disorders. A series of benzo[7]annulen-7-amines 6 was designed by conformational restriction of ifenprodil (1). At first the benzo[7]annulen-7-one 11 was prepared in a three-step synthesis comprising of a double Knoevenagel condensation of phthalaldehyde (7) with dimethyl 3-oxoglutarate (8), hydrogenation of 9 and saponification/decarboxylation of 10. Reductive amination of the ketone 11 with primary amines and NaBH(OAc)₃ led to the secondary amines 6a–d, cis-6h and trans-6i. The tertiary amines 6e–g were obtained by S_N2-substitution of the nosylate 13. Although H-bond forming substituents in 2- and 5-position are missing, the amines 6 exhibit high affinity towards GluN2B containing NMDA receptors. A distance of four to five bond lengths between the basic amino moiety and the phenyl ring in the side chain appears to be optimal for high GluN2B affinity. The phenylcyclohexylamine cis-6h and the 4-benzylpiperidine 6g show the highest GluN2B affinities (K_i = 2.3 nM and 2.9 nM, respectively). With respect to selectivity against the PCP binding site, σ₁ and σ₂ receptors the phenylpiperazine 6f is the most promising GluN2B antagonist.     

Prevalence and patterns of nitrosatable drug use among U.S. women during early pregnancy

BACKROUND

Experimental evidence indicates that certain drugs, that are secondary or tertiary amines or amides, form N‐nitroso compounds in the presence of nitrite in an acidic environment. Nitrosatable drugs have been associated with birth defects in a few epidemiologic studies. This study describes the prevalence and patterns of nitrosatable drug use among U.S. women during early pregnancy and examines maternal factors associated with such use.

METHODS

Data were analyzed from the National Birth Defects Prevention Study and included 6807 mothers who gave birth to babies without major congenital malformations during 1997 to 2005. Information was collected by telephone interview about medication use, demographic factors, and maternal health. Drugs taken during the first trimester were classified according to nitrosatability, amine and amide functional groups, and primary indication of use.

RESULTS

Approximately 24% of the women took one or more nitrosatable drugs during the first trimester, including 12.4%, 12.2%, and 7.6% who respectively took secondary amines, tertiary amines, or amides. Five of the ten most commonly taken drugs were available over the counter. Women who were non‐Hispanic white (29.5%), with 1 year or more college education (27.3%) or 40 years or older (28.8%) had the highest prevalence of use. Supplemental vitamin C, an inhibitor of nitrosation, was not taken by 41.6% and 19.3% of nitrosatable drug users during the first and second months of pregnancy, respectively.

CONCLUSIONS

In this U.S. population, ingestion of drugs classified as nitrosatable was common during the first trimester of pregnancy, especially among non‐Hispanic white, more educated, and older mothers. Birth Defects Research (Part A) 2011. © 2011 Wiley‐Liss, Inc.     

Blastomeres aggregation as an efficient alternative for trophoblast culture from porcine parthenogenetic embryos

Zona pellucida free (ZPF) oocytes were cultured after electrical activation to allow blastomeres aggregation and compared to ZP intact (ZPI) oocytes. In feeder‐dependent conditions, the trophoblast attachment and primary outgrowths were significantly higher in ZPF than in ZPI groups. In feeder‐free conditions, trophoblast attachment and typical morphological trophoblast primary outgrowths were observed in ZPF group. The primary colonies derived from the ZPF embryos in both culture conditions were able to establish secondary and tertiary colonies and showed mRNA expression of CDX2, TEAD4 and KRT8 as trophoblast markers, while outgrowths from the ZPI embryos could not grow beyond primary colonies.     

Reduced Impact of Diabetes Clinic Referral on High-Frequency Emergency Department Users

Objective: The patterns of emergency department (ED) visits in patients with diabetes are not well understood. The Emergency Department Diabetes Rapid-referral Program (EDRP) allows direct booking of ED patients presenting with urgent diabetes needs into a diabetes specialty clinic within 1 day of ED discharge. The objective of this secondary analysis was to examine characteristics of patients with diabetes who have frequent ED visits and determine reasons for revisits.Methods: A single-center analysis was conducted comparing patients referred to the EDRP (n = 420) to historical unexposed controls (n = 791). The primary outcome was the proportion of patients in each frequency group of ED revisits (none, 1 to 3 [infrequent], 4 to 10 [frequent], or >10 [superfrequent]) in the year after the ED index visit. Secondary outcomes were hospitalization rates and International Classification of Diseases–Ninth Revision (ICD-9) diagnoses at ED revisits.Results: Superfrequent users, responsible for >20% of total ED visits, made up small but not significantly different proportions of EDRP and control populations, 3.6% and 5.2%, respectively. Superfrequent groups had lower hospital admission rates at ED revisits compared to frequent groups. Mental health disorders (including substance abuse) were the primary, secondary, or tertiary ICD-9 codes in 30.6% (95% confidence interval [CI], 27.7% to 33.5%) and 6.6% (95% CI, 5.1% to 8.2%) in the superfrequent and infrequent groups, respectively.Conclusion: Direct access to diabetes specialty care from the ED is effective in reducing ED recidivism but not amongst a small subgroup of superfrequent ED users. This group was more likely to have mental health disorders recorded at ED revisits, suggesting that more comprehensive approaches are needed for this population.Abbreviations: EDRP = Emergency Department Diabetes Rapid-referral Program; ED = emergency department; HbA1c = hemoglobin A1c; ICD-9 = International Classification of Diseases–Ninth Revision     

Nocathiacin analogs: Synthesis and antibacterial activity of novel water-soluble amides

Novel water-soluble amide analogs were synthesized from nocathiacin I (1) through the formation of the carboxylic acid intermediate followed by coupling to primary or secondary amines. Several compounds with potent antibacterial activity and adequate water solubility were identified. Of these, compound 19 was selected for more extensive evaluation because of its excellent in vitro antibacterial activity and in vivo efficacy, as well as clean off-target screening.     

Design,synthesis of novel Triazolones and bis-Triazolones derivatives under ultrasound irradiation and evaluation as potent angiotensin converting enzyme (ACE) inhibitors

The condensation of several primary amines and diamines with various N¹-ethoxycarbonyles N¹-tosylhydrazonates (1a-b), triazolones (2) and bis-triazolone (3) resulted in ethanol under ultrasound irradiation. Compared with the conventional methods, the main advantages of the present procedure are milder conditions, shorter reaction time and higher yields. The newly synthesized compounds were evaluated for angiotensin I-converting enzyme (ACE) inhibition. The results were compared to Captopril as a reference drug. Compounds 3b, 2h, 3a, 2d, and 2f showed not only inhibition activity with IC₅₀ values of 0.162, 0.253, 0.253, 0.281 and 0.382 µM, respectively, but also minimal toxicity. The docking of chemical compounds in the ACE active site showed possible inhibitory effect of all compounds on the catalytic activity of the enzyme, which would satisfactorily explain the anti-hypertensive effect of these compounds.     

Stereochemistry of Internucleotide Bond Formation by the H-Phosphonate Method. 5. The Role of Brønsted and H-Bonding Base Catalysis in Ribonucleoside H-Phosphonate Condensation—Chemical and Stereochemical Consequences

Efficiency and stereoselectivity of condensations of ribonucleoside 3′-H-phosphonates with ethanol promoted by pivaloyl chloride were investigated as a function of tertiary amines used. Side reactions leading to an increased demand for the condensing agent were identified as derived from an attack of the pivalate anion at carbonyl centers of reactive pivaloyl derivatives. The conditions that secured quantitative yields of H-phosphonate diester condensations were assessed. Several tertiary amines promoted condensations with stereoselectivity higher than that observed for pyridine derivatives. A correlation between diastereoselectivity of the product formation and Brønsted and H-bonding basicities of the amine used was found.     

Preparation and bactericidal activity of oxidation derivatives of austroeupatol,an ent-nor-furano diterpenoid of the labdane series from Austroeupatorium inulifolium

From aerial parts of Austroeupatorium inulifolium was obtained austroeupatol (1). The treatment of 1 with IBX generated the ketone 2 and keto-aldehyde 3. Due to the structural features of 1, the hydroxy group corresponding to the primary alcohol (at C-19) is less reactive than the oxymethine hydroxy groups of the structure. The oxidative cleavage of 1 produced the hemiacetal 4, since this reaction is quantitative and only this compound was detected, was proposed a reaction mechanism that involves the formation of a transition state that explain the generation of 4. The bactericidal activity of these oxidation derivatives was evaluated against four (4) bacterial strains [two Gram-positive (+) and two Gram-negative (-)]: Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa.