JOURNAL OF TEXTURE STUDIES, Issue 4 2004
E.L. PARMER JR.
ABSTRACT The objective of this study was to establish conditions for the texturization of soy protein isolate and peanut flour mixture using a single-screw extruder. The effects of feed moisture, screw-speed, and barrel temperature on the characteristics of the texturized products were studied. Feed moisture was the most important factor affecting the texture. Feeding ingredients with 22% moisture had the highest water absorption and expansion indices, and Hunter L value (P < 0.05). When the screw speed was above 180 RPM, the meat analog had a 12% decrease in the expansion index and a 5% decrease in moisture content (P < 0.05). When the barrel temperature was increased to 165C, there was a 12% decrease in the water absorption index, and a 23% decrease in the expansion index of the meat analogs (P < 0.05). Overall, an acceptable meat analog could be successfully produced with 22% moisture in the raw ingredient, screw speed at 140 RPM, and barrel temperatures at 150, 155, and 160C for the three temperature zones respectively. [source]

Preparation and Structure of Oligomeric Iodosylbenzene Sulfate (PhIO)3·SO3: Stable and Water-Soluble Analog of Iodosylbenzene

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 27 2007
Alexey Y. Koposov
Abstract New phenyliodine(III) sulfate (PhIO)3·SO3, which has a complex polymeric structure of the trimeric iodosylbenzene units linked by sulfate anions, can be conveniently prepared by treatment of (diacetoxy)iodobenzene with sodium bisulfate in the presence of water. This sulfate can find practical application as a readily available, stable, and water-soluble hypervalent iodine reagent with a reactivity pattern similar tothat of iodosylbenzene. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source]

New Solutions to the C-12,13 Stereoproblem of Epothilones B and D; Synthesis of a 12,13-Diol-Acetonide Epothilone B Analog

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 15 2006
Tanja Gaich
Abstract New approaches are described to the synthesis of epothilone B and a 12,13-diol-acetonide derivative. Specifically the (12Z) double bond is formed quantitatively by a silicon-tethered ring-closing metathesis (RCM) reaction with 85,% selectivity. Alternatively, a direct route to the 12,13-epoxide by cyclization of a 12,13-diol has been developed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source]

Novel diadenosine polyphosphate analogs with oxymethylene bridges replacing oxygen in the polyphosphate chain

FEBS JOURNAL, Issue 6 2009
Potential substrates and/or inhibitors of Ap4A hydrolases
Dinucleoside polyphosphates (NpnN,s; where N and N, are nucleosides and n = 3,6 phosphate residues) are naturally occurring compounds that may act as signaling molecules. One of the most successful approaches to understand their biological functions has been through the use of NpnN, analogs. Here, we present the results of studies using novel diadenosine polyphosphate analogs, with an oxymethylene group replacing one or two bridging oxygen(s) in the polyphosphate chain. These have been tested as potential substrates and/or inhibitors of the symmetrically acting Ap4A hydrolase [bis(5,-nucleosyl)-tetraphosphatase (symmetrical); EC 3.6.1.41] from E. coli and of two asymmetrically acting Ap4A hydrolases [bis(5,-nucleosyl)-tetraphosphatase (asymmetrical); EC 3.6.1.17] from humans and narrow-leaved lupin. The six chemically synthesized analogs were: ApCH2OpOCH2pA (1), ApOCH2pCH2OpA (2), ApOpCH2OpOpA (3), ApCH2OpOpOCH2pA (4), ApOCH2pOpCH2OpA (5) and ApOpOCH2pCH2OpOpA (6). The eukaryotic asymmetrical Ap4A hydrolases degrade two compounds, 3 and 5, as anticipated in their design. Analog 3 was cleaved to AMP (pA) and ,,,-methyleneoxy-ATP (pOCH2pOpA), whereas hydrolysis of analog 5 gave two molecules of ,,,-oxymethylene ADP (pCH2OpA). The relative rates of hydrolysis of these analogs were estimated. Some of the novel nucleotides were moderately good inhibitors of the asymmetrical hydrolases, having Ki values within the range of the Km for Ap4A. By contrast, none of the six analogs were good substrates or inhibitors of the bacterial symmetrical Ap4A hydrolase. [source]

MnII(TCNE)3/2(I3)1/2,A 3D Network-Structured Organic-Based Magnet and Comparison to a 2D Analog

ADVANCED MATERIALS, Issue 23 2010
Kevin H. Stone
MnII(TCNE)3/2(I3)1/2 and MnII(TCNE)[C4(CN)8]1/2 [tetracyanoethylene (TCNE)] are organic-based magnets with 3D and 2D extended network structures with vastly different magnetic behavior. They have similar ferrimagnetic coupled layers of MnII(TCNE),, with different interlayer couplings, which lead, respectively, to net ferrimagnetic (Tc,=,171,K) and antiferromagnetic (Tc,=,68,K) order. [source]

Texture and Chemical Characteristics of Soy Protein Meat Analog Extruded at High Moisture

JOURNAL OF FOOD SCIENCE, Issue 2 2000
S. Lin
ABSTRACT: The relationships among extruder responses, texture, and protein solubility of soy protein meat analogs were studied. Soy protein isolate and wheat starch at 9:1 ratio were extruded at 60%, 65%, and 70% moisture contents and 137.8, 148.9, and 160°C cooking temperatures. The results showed that moisture content was a more important factor on the overall product texture than cooking temperature. Lower moisture content resulted in higher die pressure, harder texture, and lower total protein solubility. At a fixed moisture content, a higher cooking temperature resulted in a softer and less chewy product but only slightly changed the protein solubility. According to partial least square regression, the data from Texture Profile Analysis, protein solubility, and extruder responses correlated well and could be used to predict each other. [source]

Editorial: Glargine, a New Long-Acting Insulin Analog for Diabetic Cats

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2006
Jacquie Rand
No abstract is available for this article. [source]

Mitigating Photosensitivity of Erythropoietic Protoporphyria Patients by an Agonistic Analog of ,-Melanocyte Stimulating Hormone,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2009
Juergen H. Harms
Erythropoietic protoporphyria (EPP) is a rare hereditary disorder characterized by dermal accumulation of the photosensitizer protoporphyrin IX. Following sunlight exposure, the resulting photosensitivity is manifested first as pain, later as erythema, edema and dermal lesions. Afamelanotide (Nle4 -d-Phe7 -,-MSH), a synthetic analog of ,-melanocyte stimulating hormone and agonist of the melanocortin-1-receptor, promotes melanin synthesis, increasing skin pigmentation. This study examines the efficacy of afamelanotide in preventing symptoms in patients with EPP. A sustained-release subcutaneous implant of 20 mg afamelanotide was administered twice, with a 60-day interval to five EPP patients. Therapeutic efficacy was assessed by a photoprovocation test using standardized white light irradiation, melanin density (MD) determination and daily recording of sunlight exposure and symptoms. From Day 30 to Day 120 tolerance to photoprovocation significantly increased compared with baseline (P = 0.007) and skin MD was significantly higher than that recorded at baseline (P = 0.004). Except for two low-grade pain episodes, patients recorded no phototoxic events past Day 4 of treatment. Tolerance to natural sunlight was up to 24 times longer than prior to therapy. The findings demonstrate beneficial effects of afamelanotide in patients with EPP. Due to the limited number of patients enrolled and the design being an open-label study, confirmation by a large-scale trial is required. [source]

Therapeutic Effects of Vitamin E on Cyclic Mastalgia

THE BREAST JOURNAL, Issue 5 2009
Sousan Parsay PhD
Abstract:, Cyclic mastalgia is one of the most prevalent disorders among fertile women. To date, hormonal agents, despite their side effects, have been widely used for treatment of this ailment. This study was performed to clarify the therapeutic effects of Vitamin E (Vit E) as a safe treatment for cyclic mastalgia among fertile women. This study was conducted as a double blind clinical trial; 150 women with cyclic mastalgia, referred by three public health centers in Qazvin City in Iran, were enrolled in the trial and randomly divided into two distinct case and control groups; each containing 75 patients. The severity and duration of breast pain were measured according to both the Cardiff Breast Pain Chart and the Visual Analog Scale. Simple, chewable tablets of either Vit E or a placebo were prescribed twice a day for 4 months for case and control participants, respectively. Follow-up was performed at the end of both the second and the fourth months and, at that time, the severity, duration and side effects of intervention were evaluated. The administration of Vit E had significant curative results as tested at both the 2- and 4-month benchmarks. Chi-square testing indicated that after both 2 and 4 months of therapy, the efficacy demonstrated by the Vit E recipient case group was superior to that of the group that received a placebo. Applying the Mc Nemar Test, it also was shown that there was no significant difference in the benefits received between treatment courses of 2 versus 4 months. A 2-month prescription of Vit E has positive therapeutic effects on cyclic mastalgia. Given its lack of significant side effects, Vit E, therefore, can be considered a safe alternative to hormonal therapies currently being used in the treatment of cyclic mastalgia. [source]

Treatment of Nonparaphilic Hypersexuality in Men with a Long-Acting Analog of Gonadotropin-Releasing Hormone

THE JOURNAL OF SEXUAL MEDICINE, Issue 4 2009
Mohammad R. Safarinejad MD
ABSTRACT Introduction., Hypersexuality is one of the most embarrassing behaviors for both patients and their families and there are no effective drug treatments for this sexual inappropriateness. Aim., To evaluate the efficacy and safety of a long-acting analog of gonadotropin-releasing hormone (triptorelin) in men with nonparaphilic hypersexuality (NPH). Main Outcome Measures., Primary outcome measure was the frequency of intercourse. The designated secondary outcome measures were the changes in International Index of Erectile Function (IIEF) questionnaire and responses to the questions from the IIEF in the preceding month: question 11, "How often have you felt sexual desire?" and question 12, "How would you rate your level of sexual desire"? Methods., Seventy-six men (mean age 44.4 years) with NPH were treated with monthly intramuscular injections of 3.75 mg of triptorelin for an indefinite period. During treatment, serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, testosterone (T), and free testosterone (fT), were measured monthly, and bone mineral density every 6 months. Results., The mean sexual attempts decreased from 7.6 ± 1.4 per day at baseline to 4.2 ± 1.2 (P = 0.001), 1.2 ± 0.4 (P = 0.001), and <1 per week (P = 0.0001), after 6-, 12-, and 24-month treatment, respectively. The mean scores for questions 11 and 12, improved from 6.8 ± 1.1, and 6.6 ± 1.2, at baseline to 0.7 ± 0.4 (P = 0.0001), and 0.7 ± 0.5 (P = 0.0001), at 24-month treatment, respectively. Positive response to triptorelin was significantly associated with severity of baseline hypersexuality (r = ,0.62, P = 0.01), and treatment duration (r = 0.78, P = 0.001). These beneficial effects persisted 6 months in all men who were treated for at least 24 months. The serum LH and FSH concentrations begun to decrease after two doses of triptorelin. After 3 months, serum T, and fT levels decreased by 50% in 65 (85.5%) of patients (P = 0.01). Conclusions., Triptorelin was very effective and well tolerated in men with NPH. Further studies are needed to replicate our results. Safarinejad MR. Treatment of nonparaphilic hypersexuality in men with a long-acting analog of gonadotropin-releasing hormone. J Sex Med **;**:**,**. [source]

Synthesis and biological activity of GnRH antagonists modified at position 3 with 3-(2-methoxy-5-pyridyl)-alanine,

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 2 2005
M.P. Samant
Abstract:, Degarelix is a potent very long-acting GnRH antagonist after subcutaneous administration. In this paper, we describe the synthesis of two analogs of degarelix incorporating racemic 3-(2-methoxy-5-pyridyl)-alanine (2-OMe-5Pal, 5) at position 3. The two diastereomers were separated by reverse-phase high-performance liquid chromatography (RP-HPLC) and the absolute stereochemistry at position 3 in the peptides was determined by enzymatic digestion with proteinase K. These analogs were tested in vitro for their ability to antagonize the GnRH receptor and in vivo for duration of action in a castrated male rat assay. Analog 7 with D2-OMe-5Pal was potent in vitro (IC50 = 5.22 nm); however, analog 8 with L2-OMe-5Pal at position 3 in degarelix lost potency as an antagonist of the human GnRH receptor (IC50 = 36.95 nm). Both the analogs were found to be short-acting in vivo. [source]

Comment on "Disproving a Silicon Analog of an Alkyne with the Aid of Topological Analyses of the Electronic Structure and Ab Initio Molecular Dynamics Calculations"

CHEMPHYSCHEM, Issue 4 2006
Gernot Frenking Prof. Dr.
Bond order of a silicon-silicon bond (1): The statement that the recently synthesized compound RSiSiR (1) (RSi[C(SiMe3)3]2CHMe2) has rather a double than a triple bond is challenged. Arguments are given which support the interpretation of the bonding situation in terms of two donor,acceptor bonds which are enhanced by one , bond (see picture). [source]

Disproving a Silicon Analog of an Alkyne with the Aid of Topological Analyses of the Electronic Structure and Ab Initio Molecular Dynamics Calculations

CHEMPHYSCHEM, Issue 9 2005
Carlo A. Pignedoli Dr.
Abstract A silicon compound has recently been synthesized that was claimed to exhibit the first realization of a silicon,silicon triple bond. We debate this classification on the basis of a thorough investigation of the nature of the chemical bond, using the rigorous topological analysis of the electron density as developed in Bader's atoms-in-molecules theory, that of the electron localization function and the related orbital-independent definitions of the bond order. Our results refer both to the ground-state geometry and to nonequilibrium configurations, which are accessed by the system in a room-temperature ab initio molecular dynamics simulation. We also use the reciprocal compliance force constant as an independent chemical descriptor. All the above procedures are in agreement and do not support the classification of the silicon,silicon central bond as triple. The characterization which consistently emerges from the present study is one in which two electron pairs participate in the bonding and the other pair belongs mainly to nonbonding regions. [source]

Syntheses of Triostin A Antibiotic and Nucleobase-Functionalized Analogs as New DNA Binders

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 28 2009
Anmol Kumar Ray
Abstract A total synthesis of the natural product triostin A, wherein the N -methylated depsipeptide scaffold is constructed by solution-phase peptide chemistry followed by disulfide formation and macrocyclization, is described. Finally, the quinoxalines were attached to provide the DNA bisintercalator. Analogs of triostin A were obtained by the successive functionalization of the cyclic depsipeptide with pyrimidine or purine recognition units. The attachment of functional units was achieved by the orthogonal protection of the respective side chain amino functionalities. The nucleobase-functionalized triostin analogs have the potential to recognize double-stranded DNA by hydrogen bonding. The interaction with DNA was investigated by UV spectroscopy and fluorescence intercalator displacement. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]

Two New Endiandric Acid Analogs, a New Benzopyran, and a New Benzenoid from the Root of Beilschmiedia erythrophloia

HELVETICA CHIMICA ACTA, Issue 11 2008
Ping-Shin Yang
Abstract Phytochemical investigation of the root of Beilschmiedia erythrophloia led to the isolation and structural elucidation of two new endiandric acid analogs, endiandric acids I and J (1 and 2, resp.), a new benzopyran, dehydrooligandrol methyl ether (3), and a new benzenoid, farnesylol (4), together with six known compounds. Their structures were established on the basis of extensive 1D- and 2D-NMR analyses in combination with HR-MS experiments. [source]

Isolation and Structure Elucidation of Enniatins L, M1, M2, and N: Novel Hydroxy Analogs

HELVETICA CHIMICA ACTA, Issue 8 2004
Pornrapee Vongvilai
Four new cyclohexadepsipeptides, enniatins L (1), M1 (2), M2 (3), and N (4), have been isolated from an unidentified fungus (BCC 2629), together with the known enniatins B (5), H (6), and I (7), MK1688 (8), and enniatin B4 (9). Compounds 1,4 are the first enniatin analogs with an OH group at the side chain of one of the 2-hydroxycarboxylic acid residues. The structures of 1,4 were elucidated by spectroscopic means and by X-ray crystallography. [source]

Synthesis and Properties of Oligodeoxynucleotide Analogs with Bis(methylene) Sulfone Bridges

HELVETICA CHIMICA ACTA, Issue 9 2003
Bernd Eschgfäller
A convergent, solution-phase synthesis was developed for the bis(methylene) sulfone-bridged oligodeoxynucleotide analogs (SNA) 5,-d(HOCH2 -Tso2Tso2Tso2Cso2Tso2Tso2Tso2T-CH2SO)-3, (35b) and 5,-d(HOCH2 -Tso2Tso2Tso2Tso2Tso2Tso2Tso2T-CH2SO)-3, (34c) (SO2 corresponds to CH2SO2CH2 instead of OP(O)(O,)(O). In these, the phosphodiester linkages are replaced by non-ionic bis(methylene) sulfone linkers. The general strategy involved convergent coupling of 3,,5,-bishomo- , - D -deoxyribonucleotide analogs functionalized at the 6,-end (CH2C(5,)) as bromides or mesylates and at the CH2C(3,) position as thiols, with the resulting thioether being oxidized to the corresponding sulfone. A single charge was introduced at the terminal CH2C(3,) position of the octamers to increase their solubility in water. During the synthesis, it became apparent that the key intermediates generated secondary structures through either folding or aggregation in a variety of solvents. This generated unusual reactivity and was unique for very similar structures. For example, although the dimeric thiol d(BzOCH2 -Tso2C-CH2SH) (14b) was a well-behaved synthetic intermediate, the tetrameric thiol d(TrOCH2 -Tso2Tso2Tso2toC-CH2SH) derived from the corresponding thioacetate was rapidly converted to a disulfide by very small amounts of oxidant (28,29, Scheme,6), while the analogous tetrameric thiol d(BzOCH2 -Tso2TsTso2T-CH2SH) (26), differing only by a single heterocycle, was oxidized much more slowly (Bz=PhCO, Tr=Ph3C, to=2-MeC6H4CO (at N4 of dc)). The sequence-dependent reactivity, well known in many classes of natural products (including polypeptides), is not prominent in natural oligonucleotides. These results are discussed in light of the proposal that the repeating negative charge in nucleic acids is key to their ability to serve as genetic molecules, in particular, their capability to support Darwinian evolution. The ability of 5,-d(HOCH2 -Tso2Tso2Tso2Cso2Tso2Tso2Tso2T-CH2SO)-3, (35b) to bind as a third strand to duplex DNA was also examined. No triple-helix-forming propensity was detected in this molecule. [source]

New Long-Chain Esters and Adenine Analogs from the Leaves of Formosan Bridelia balansae

HELVETICA CHIMICA ACTA, Issue 7 2003
Yeh-Hsin Tsai
Six new compounds, including the two long-chain esters balansenate I (=6,8,11-trimethyldodecanoic acid (2E)-3-methylhexadec-2-enyl ester; 1) and balansenate II (=10,12,15-trimethylhexadedecanoic acid (2E)-3-methylhexadec-2-enyl ester; 2), the eburicane-like triterpenoid bridelone (=hexadecahydro-4,4,10,13,14-pentamethyl-17-(5-methyl-1,4-dimethylenehexyl)-3H -cyclopenta[a]phenanthren-3-one; 3), the ,deimino-xanthine', bridelonine (=5-(3-methylbut-2-enyl)pyrrolo[3,4- d]imidazole-4,6(1H,5H)-dione; 6), and the two adenine analogs 9-(3-methylbut-2-enyl)adenine (7) and 1-(3-methylbut-2-enyl)adenine (8), besides three known compounds, i.e., N6 -(3-methylbut-2-enyl)adenine (4), 3-(3-methylbut-2-enyl)adenine (5), and adenine (9), were isolated from the leaves of Formosan Bridelia balansae. The novel skeleton of 6 consists of a fused pyrrolidine-2,5-dione and imidazole moiety. The already known adenines 7 and 8 were isolated for the first time from a plant. The structures of the isolated compounds were elucidated by spectroscopic analyses. [source]

Synthesis and Evaluation of Chromogenic and Fluorogenic Analogs of Glycerol for Enzyme Assays

HELVETICA CHIMICA ACTA, Issue 7 2003
Maria González-García
The branched glycerol analogs 1 and 2 were prepared. Mono-ester derivatives of these triols undergo a chromogenic or fluorogenic reaction in the presence of NaIO4. In contrast, both the diesters and the triols are themselves not chromogenic or fluorogenic. Diester derivatives of these triols can be used as probes for lipases. The tris-phosphate derivative of 1 is a fluorogenic substrate for various phosphatases. [source]

Comparison of the Relative Reactivities of the Triisopropylsilyl Group With Two Fluorous Analogs

ADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 7-8 2009
Amador Garcia Sancho
Abstract The relative stabilities of two fluorous analogs, diisopropyl(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10- heptadecafluorodecyl)silyl and diisopropyl- (4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafluoroundecyl)silyl [C8F17(CH2)nSi(i- Pr)2, where n=2 or 3], of the standard triisopropylsilyl (TIPS) group are compared in the setting of alcohol protection. The fluorous silyl groups can be installed under standard conditions in comparable yields to the TIPS group, but the derived fluorous silyl ethers are more labile than TIPS ethers towards cleavage by both acids and fluoride. [source]

Differential Effects of Vitamin D Analogs on Vascular Calcification,,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2007
Anna Cardús
Abstract We tested the effects of calcitriol and its analog paricalcitol on VSMC calcification in vitro and in vivo. For that reason, cells and animals with five-sixths nephrectomy were treated with both compounds. Calcitriol, but not paricalcitol, increased VSMC calcification in vitro and in vivo independently of calcium and phosphate levels. This increase in calcification was parallel to an increase in the RANKL/OPG ratio. Introduction: Vascular calcification is a common finding in patients with endstage renal disease. Furthermore, those patients often present secondary hyperparathyroidism, partly because of a decrease of calcitriol synthesis on the kidney. Thus, one of the main therapeutic options is to treat those patients with calcitriol or analogs. However, this treatment presents unwanted side effects, such as increases in vascular calcification. Materials and Methods: We tested the effect on vascular smooth muscle cell (VSMC) calcification of calcitriol and one of its analogs, paricalcitol, in vitro and in vivo in animals with endstage renal disease. Results: Calcitriol increased calcification of VSMCs cultured in calcification media. This effect was not present when cells were incubated with paricalcitol. Furthermore, only cells incubated with calcitriol showed an increased RANKL/ osteoprotegerin (OPG) expression. Animals with renal failure treated with hypercalcemic doses of calcitriol and paricalcitol showed an increase in systolic blood pressure. However, diastolic blood pressure only raised significantly in those animals treated with paricalcitol. This effect led to a significant increase in pulse pressure in animals treated with calcitriol. The increase in pulse pressure was likely caused by the extensive calcification observed in arteries of animals treated with calcitriol. This increase in calcification was not seen in arteries of animals treated with paricalcitol, despite having similar levels of serum calcium and phosphorus as animals treated with calcitriol. Furthermore, the decreases in serum PTH levels were similar in both treatments. Conclusions: We conclude that paricalcitol has a different effect than calcitriol in VSMC calcification and that this could explain part of the differences observed in the clinical settings. [source]

Structure,activity relationship of an antibacterial peptide, maculatin 1.1, from the skin glands of the tree frog, Litoria genimaculata

JOURNAL OF PEPTIDE SCIENCE, Issue 7 2004
Takuro Niidome
Abstract Maculatin 1.1 (Mac) is a cationic antibacterial peptide isolated from the dorsal glands of the tree frog, Litoria genimaculata, and has a sequence of GLFGVLAKVAAHVVPAIAEHF-NH2. A short peptide lacking the N -terminal two residues of Mac was reported to have no activity. To investigate the structure,activity relationship in detail, several analogs and related short peptides of Mac were synthesized. CD measurement showed that all the peptides took more or less an ,-helical structure in the presence of anionic lipid vesicles. Analogs which are more basic than Mac had strong antibacterial and hemolytic activities, while short peptides lacking one or two terminal residues exhibited weak or no activity. Outer and inner membrane permeabilization activities of the peptides were also reduced with shortening of the peptide chain. These results indicate that the entire chain length of Mac is necessary for full activity, and the basicity of the peptides greatly affects the activity. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source]

Vitamin D and Vitamin D Analogs as Cancer Chemopreventive Agents

NUTRITION REVIEWS, Issue 7 2003
DABT, Kathryn Z. Guyton PhD
Epidemiologic studies have associated vitamin D, attained through nutrition and sun exposure, with reduced cancer risk. Although dose-limiting hypercalcemia has limited the use of natural vitamin D in cancer prevention, several promising new synthetic vitamin D analogs (deltanoids) are under development. Examples are KH-1060, EB1089, 1 , -hydroxyvitamin D5, vitamin D2, and QW-1624F2-2. Clinical targets for deltanoids include colon, prostate, and breast. Studies to elucidate the molecular mechanisms underlying the observed efficacy of deltanoids are ongoing. The vitamin D receptor, a steroid/thyroid receptor superfamily member, appears to control most deltanoid effects on proliferation, apoptosis, differentiation, and angiogenesis. [source]

Hydroxylated Analogs of Mexiletine as Tools for Structural-Requirements Investigation of the Sodium Channel Blocking Activity

ARCHIV DER PHARMAZIE, Issue 6 2010
Alessia Catalano
Abstract [2-(2-Aminopropoxy)-1,3-phenylene]dimethanol 1 and 4-(2-aminopropoxy)-3-(hydroxymethyl)-5-methylphenol 2, two dihydroxylated analogs of mexiletine , a well known class IB anti-arrhythmic drug , were synthesized and used as pharmacological tools to investigate the blocking-activity requirements of human skeletal muscle, voltage-gated sodium channel. The very low blocking activity shown by newly synthesized compounds corroborates the hypothesis that the presence of a phenolic group in the para-position to the aromatic moiety and/or benzylic hydroxyl groups on the aromatic moiety of local anesthetic-like drugs impairs either the transport to or the interaction with the binding site in the pore of Na+ channels. [source]

Novel Fused Pyrrole Heterocyclic Ring Systems as Structure Analogs of LE 300: Synthesis and Pharmacological Evaluation as Serotonin 5-HT2A, Dopamine and Histamine H1 Receptor Ligands

ARCHIV DER PHARMAZIE, Issue 2 2010
Sherif A. F. Rostom
Abstract LE 300 represents a structurally novel type of antagonists acting preferentially at the dopamine D1/D5 receptors and the serotonin 5-HT2A receptor. This compound consists of a ten-membered central azecine ring fused to an indole ring on one side and a benzene moiety on the other side. To estimate the importance of the indole and / or phenyl moieties in this highly active benz-indolo-azecine, both rings were removed and replaced with a 1H -pyrrole counterpart. Accordingly, some new analogs of LE 300 namely, pyrrolo[2,3- g]indolizine, pyrrolo[3,2- a]quinolizine rings and their corresponding dimethylpyrrolo[2,3- d]azonine, and dimethylpyrrolo[2,3- d]azecine were synthesized to be evaluated for their activity at the 5-HT2A and dopamine D1, D2L, D4, D5 receptors in relation to LE 300. In addition, their activity at the H1 -histamine receptors was also determined. The results suggested that the rigid pyrrolo[2,3- g]indolizine 7 and pyrrolo[3,2- a]quinolizine 8 analogs lacked biological activity in the adopted three bioassays. However, their corresponding flexible pyrrolo[2,3- d]azonine 11 and pyrrolo[2,3- d]azecine 12 derivatives revealed weak partial agonistic activity and weak antagonistic potency at the serotonin 5-HT2A and histamine H1 receptors, respectively. Meanwhile, they showed no affinity to any of the four utilized dopamine receptors. Variation in ring size did not contribute to a significant influence on the three tested bioactivities. Removal of the hydrophobic moiety (phenyl ring) and replacement of the indole moiety with a 1H -pyrrole counterpart led to a dramatic alteration in the profile of activity of such azecine-type compounds. [source]

Synthesis and Antibacterial Activities of Eperezolid Analogs with Glycinyl Substitutions

ARCHIV DER PHARMAZIE, Issue 7 2009
Xiao-Jun Wang
Abstract A series of eperezolid analogs with glycinyl substitutions were prepared and their antibacterial activities were studied against a panel of susceptible and resistant Gram-positive bacteria. The compounds with N -arylacyl or N -heteroarylacyl glycinyl structural units showed good antibacterial activities. The compounds 11b, 11c, and 11e were twofold more active than linezolid against Staphylococcus epidermidis and Enterococcus faecalis. Several pyridine analogs were also prepared and found to have poor antibacterial activity against most of the tested Gram-positive bacteria, however, one of the compounds 12e showed very high activity against Enterococcus faecalis. [source]

Conformationally Constrained Analogs of N -Substituted Piperazinylquinolones: Synthesis and Antibacterial Activity of N -(2,3-Dihydro-4-hydroxyimino-4H -1-benzopyran-3-yl)-piperazinylquinolones

ARCHIV DER PHARMAZIE, Issue 7 2009
Saeed Emami
Abstract A series of novel quinolone agents bearing a particular bulky and conformationally constrained bicyclic substituent (2,3-dihydro-4-hydroxyimino-4H -1-benzopyran-3-yl- moiety) on the piperazine ring of 7-piperazinyl quinolones (norfloxacin, enoxacin, ciprofloxacin, and levofloxacin) were synthesized and evaluated against a panel of Gram-positive and Gram-negative bacteria. Among these derivatives, ciprofloxacin counterpart 9c, highly inhibited the tested Gram-positive bacteria, superior to that of the reference drugs, and displayed antibacterial activity at non-cytotoxic concentrations. [source]

Development of a New Pharmacophore Model That Discriminates Active Compstatin Analogs

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 4 2008
Ting-Lan Chiu
Compstatin and its active peptide analogs can potentially be used for therapeutic purposes because their binding to the third component of complement prohibits its conversion into the proteolytically activated form of the third component of complement, thus inhibiting complement cascades in all three complement pathways. Mallik and Morikis built three quasi-dynamic pharmacophore models for compstatin peptide analogs before, but only nine compstatin peptide analogs were incorporated in their study and the most active compstatin analog had only medium inhibitory activity. Since then, many more compstatin analogs have been synthesized and their inhibitory activities tested. Furthermore, the X-ray structure of AcCompNH2-V4W-H9A bound to the third component of complement has become available (PDB ID: 2QKI). In this paper, we utilized all the new information and built a new pharmacophore model using a distinct approach. Our model demonstrated good performance in a separate test set of 82 compstatin analogs: it accurately identified 70% of the analogs of medium or high inhibitory activities and misclassified only 8.5% of the analogs of low or no inhibitory activities. The results proved our pharmacophore model to be a filter of great sensitivity and specificity. [source]

Synthesis of Novel Peptide Inhibitors of Thrombin-induced Platelet Activation

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 5 2006
Fernanda M. Burke
Inhibitors of the activation of platelet aggregation have promise as important therapeutic agents for the management of acute coronary syndrome (ACS). Platelet activation by thrombin, a serine protease, occurs by binding to and cleavage of the extracellular N-terminal domains of protease-activated receptors 1 and 4 (PAR1 and PAR4). The proteolysis of the PARs exposes new tethered ligands that then signal through transmembrane domains to initiate platelet activation as a downstream effect. A pentapeptide cleavage product of bradykinin with the sequence Arg-Pro-Pro-Gly-Phe serves as a thrombin inhibitor by blocking , - and , -thrombin-induced platelet aggregation. Analogs of RPPGF have been prepared that result in improved inhibition of thrombin activation of platelets. Specific amino acid residues required for activity against platelet aggregation have been identified, and a lead compound, rOicPaPhe(p -Me)-NH2 (FM19), has been developed. FM19, which completely inhibits threshold , -thrombin-induced platelet aggregation at a concentration of 16 ± 4 ,m, represents an important lead compound in the development of inhibitors of thrombin-mediated platelet aggregation for treatment of ACS. [source]

Cellular Analysis of Disorazole C1 and Structure,Activity Relationship of Analogs of the Natural Product

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 1 2006
Peter Wipf
Structure,activity analyses of synthetic disorazole C1 and eight of its analogs indicate that the presence of a vinyl oxirane moiety or a tetraene sequence is not necessary for potent cytotoxic and antimitotic properties. Using an automated multiparameter fluorescence-based cellular assay to simultaneously probe the effects of disorazole analogs on cellular microtubules, mitotic arrest, and cytotoxicity, we found that disorazole C1 enhanced the mitotic index and chromatin condensation and arrested cells in the G2/M phase of the cell cycle. All structural analogs and synthesis precursors of disorazole C1 were at least two orders of magnitude less potent than the parent compound, thus indicating that both the functional group array and the three-dimensional conformation of the parent compound are critical for interaction with the biological target. We conclude that disorazole C1 is a potent inducer of mitotic arrest and hypothesize that this biological activity may be mediated by microtubule perturbation. [source]