Oxidation of Two Hydroxylated Ochratoxin A Metabolites by Alcohol Dehydrogenase

(4R)-4-hydroxyochratoxin A, (4S)-4-hydroxyochratoxin A, and 10-hydroxyochratoxin A, all formed from ochratoxin A, were incubated with alcohol dehydrogenase in the presence of NAD. Only (4R)-4-hydroxyochratoxin A and 10-hydroxyochratoxin A acted as substrates for the enzyme. K_m and turnover number for 10-hydroxyochratoxin A were 110 μM and 0.1 s⁻¹, respectively.     

Isolation, identification, synthesis and biological activity of volatile compounds from the heads of Atta ants

S-(+)-4-methyl-3-heptanone has been identified as the principal alarm pheromone of Atta texana and Atta cephalotes. Both enantiomers of 4-methyl-3-heptanone have been synthesized and their biological activities have been compared on both species of ants. Comparison of the geometric averages of response ratios, at threshold concentration levels on A. texana, showed S-(+)-4-methyl-3-heptanone to be about 100 times more active than the (?) enantiomer. A similar analysis also showed no inhibition of the activity of S-(+)-4-methyl-3-heptanone by the (?) enantiomer. A less rigorous study on A. cephalotes showed S-(+)-4-methyl-3-heptanone to be about 210 times more active than R-(?)-4-methyl-3-heptanone.Both ant species produce 3-octanone, possible trace amounts of 3-octanol, and both diastereomers of 4-methyl-3-heptanol. A. texana also produces (+)-2-heptanol, 2-heptanone, and 3-heptanol. A. cephalotes contains trace amounts of 2-heptanone.     

Cardiovascular protective flavonolignans and flavonoids from Calamus quiquesetinervius

Tricin-type flavonolignans, (2S)-dihydrotricin 4′-O-(erythro-β-guaiacylglyceryl) ether, (2S)-dihydrotricin 4′-O-(threo-β-guaiacylglyceryl) ether, (2S)-dihydrotricin 4′-O-(threo-β-4-hydroxyphenylglyceryl) ether, tricin 4′-O-(erythro-β-4-hydroxyphenylglyceryl) ether, tricin 4′-O-(threo-β-4-hydroxylphenylglyceryl) ether, and (2S)-dihydrotricin 4′-O-(β-6′′-methoxy-4′′-oxo-chroman-3′′-yloxy) ether namely calquiquelignan A–F, respectively, were isolated and characterized from the EtOAc extract of Calamus quiquesetinervius. Additionally, six known phenolic compounds, including dihydrotricin, tricin, salcolin A, p-hydroxybenzoic acid, (2S, 3S)-trans-dihydrokapempferol and (2S)-naringenin, were also obtained and identified from the extract. Structures of the flavonolignans were assigned based on spectroscopic analyses that included 1D and 2D NMR spectroscopic techniques, such as HMQC, HMBC, and NOESY. Bioassay results showed that calquiquelignan A, dihydrotricin and (2S)-naringenin exhibited significant vasodilatory potencies, as indicated by 60.3%, 80.3% and 60.9% relaxations, respectively, at 100 μM. Salcolin A showed potent platelet aggregation inhibition, compared with aspirin. Most of the tricin-type derivatives (calquiquelignan A–B, dihydrotricin and tricin) also exhibited more potent hydroxyl radical (OH) scavenging activity than trolox as characterized by the ultraweak chemiluminescence assay.     

Synthesis of novel substituted pyrazole-5-carbohydrazide hydrazone derivatives and discovery of a potent apoptosis inducer in A549 lung cancer cells

A series of novel 3-aryl-1-(4-tert-butylbenzyl)-1H-pyrazole-5-carbohydrazide hydrazone derivatives were synthesized and the effects of all the compounds on A549 cell growth were investigated. The results showed that all compounds had inhibitory effects on the growth of A549 lung cancer cells and compound (E)-1-(4-tert-butylbenzyl)-N′-(1-(5-chloro-2-hydroxyphenyl) ethylidene)-3-(4-chlorophenyl)-1H-pyrazole-5-carbohydrazide (3e) possessed the highest growth inhibitory effect and induced apoptosis of A549 lung cancer cells.     

Effects of variations in the APOA1/C3/A4/A5 gene cluster on different parameters of postprandial lipid metabolism in healthy young men

The APOA1/C3/A4/A5 gene cluster encodes important regulators of fasting lipids, but the majority of lipid metabolism takes place in the postprandial state and knowledge about gene regulation in this state is scarce. With the aim of characterizing possible regulators of lipid metabolism, we studied the effects of nine single nucleotide polymorphisms (SNPs) during postprandial lipid metabolism. Eighty-eight healthy young men were genotyped for APOA1 -2630 (rs613808), APOA1 -2803 (rs2727784), APOA1 -3012 (rs11216158), APOC3 -640 (rs2542052), APOC3 -2886 (rs2542051), APOC3 G34G (rs4520), APOA4 N147S (rs5104), APOA4 T29T (rs5092), and A4A5_inter (rs1263177) and were fed a saturated fatty acid-rich meal (1g fat/kg of weight with 60% fat, 15% protein and 25% carbohydrate). Serial blood samples were extracted for 11 h after the meal. Total cholesterol and fractions [HDL-cholesterol, LDL-cholesterol, trifacylglycerols (TGs) in plasma, TG-rich lipoproteins (TRLs) (large TRLs and small TRLs), apolipoprotein A-I and apolipoprotein B] were determined. APOA1 -2803 homozygotes for the minor allele and A4A5_inter carriers showed a limited degree of postprandial lipemia. Carriers of the rare alleles of APOA4 N147S and APOA4 T29T had lower APOA1 plasma concentration during this state. APOC3 -640 was associated with altered TG kinetics but not its magnitude. We have identified new associations between SNPs in the APOA1/C3/A4/A5 gene cluster and altered postprandial lipid metabolism.     

Design,synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction

Recent target validation studies have shown that inhibition of the protein interaction between annexin A2 and the S100A10 protein may have potential therapeutic benefits in cancer. Virtual screening identified certain 3,4,5-trisubstituted 4H-1,2,4-triazoles as moderately potent inhibitors of this interaction. A series of analogues were synthesized based on the 1,2,4-triazole scaffold and were evaluated for inhibition of the annexin A2–S100A10 protein interaction in competitive binding assays. 2-[(5-{[(4,6-Dimethylpyrimidin-2-yl)sulfanyl]methyl}-4-(furan-2-ylmethyl)-4H-1,2,4-triazol-3-yl)sulfanyl]-N-[4-(propan-2-yl)phenyl]acetamide (36) showed improved potency and was shown to disrupt the native complex between annexin A2 and S100A10.     

TRF4 is involved in polyadenylation of snRNAs in Drosophila melanogaster

The Saccharomyces cerevisiae poly(A) polymerases Trf4 and Trf5 are involved in an RNA quality control mechanism, where polyadenylated RNAs are degraded by the nuclear exosome. Although Trf4/5 homologue genes are distributed throughout multicellular organisms, their biological roles remain to be elucidated. We isolated here the two homologues of Trf4/5 in Drosophila melanogaster, named DmTRF4-1 and DmTRF4-2, and investigated their biological function. DmTRF4-1 displayed poly(A) polymerase activity in vitro, whereas DmTRF4-2 did not. Gene knockdown of DmTRF4-1 by RNA interference is lethal in flies, as is the case for the trf4 trf5 double mutants. In contrast, disruption of DmTRF4-2 results in viable flies. Cellular localization analysis suggested that DmTRF4-1 localizes in the nucleolus. Abnormal polyadenylation of snRNAs was observed in transgenic flies overexpressing DmTRF4-1 and was slightly increased by the suppression of DmRrp6, the 3′-5′ exonuclease of the nuclear exosome. These results suggest that DmTRF4-1 and DmRrp6 are involved in the polyadenylation-mediated degradation of snRNAs in vivo.     

Association between the interleukin-4, interleukin-13 polymorphisms and asthma: a meta-analysis

A numbers studies had been reported that the polymorphisms in the Interleukin 4 (IL-4) and Interleukin 13 (IL-13) genes were associated with susceptibility to asthma. However, the results were inconsistent and inconclusive. We carried out a meta-analysis of case–control genetic association studies to assess whether the combined data showed this association by using a genetic model-free approach. Thirty studies (total 12,781 asthma and 11,500 controls) for the IL-4 C-33T and C-589T, IL-13 C-1112T and G+2044A with asthma were included in the meta-analysis. The results indicated that there were an association between the IL-4 C-33T (P = 0.006) and C-589T (P = 0.04), IL-13 C-1112T (P = 0.002) and G+2044A (P = 0.04) and susceptibility to asthma. And the definition of asthma subgroup meta-analysis demonstrates that the IL-4 C-33T is not associated with nonatopic or atopic, and IL-4 C-589T and IL-13 C-1112T polymorphisms are not associated with atopic. In the ethnicity subgroup meta-analysis, the IL-4 ?589T (P = 0.003) and the IL-13 ?1112T (P < 0.00001) alleles are associated with asthma among Caucasian, but not on the IL-13 +2044A allele. In conclusion, IL-4 C-33T and C-589T, IL-13 C-1112T and G+2044A could be proposed as asthma susceptible SNPs. Further investigation in larger studies and meta-analysis is required.     

Collecting cultivated and wild Cucurbits in Mexico

The authors spent approximately 5 weeks in Mexico (October 13–November 15, 1979) collecting Cucurbitaceae in 5 areas: 1) Tampico- Valles- Ocampo; 2) San Luis Potosi; 3) Celaya- Queretaro; 4) Veracruz; 5) Zacatecas- Durango- Mazatlan. A few supplemental collections were made in the vicinity of Tapachula, Chiapas. A grand total of 183Cucurbita collections was made, distributed as follows:C. pepo-49;C. moschata-47;C. mixta- 41;C. ficifolia-11;C. foetidissima-13;Cucurbita sp. wild, unidentified- 22. A few collections were made in the following genera:Sechium-4;Lagenaria-2;Sicana-1;Momordica-4;Sicyos-2;Cucumis melo-2;C. anguria-1. The ecological distribution of the 4 cultivated species is reported and discussed. Seed of these materials was divided equally between the participating countries, and will be made available to interested plant breeders.     

Novel series of 3-amino-N-(4-aryl-1,1-dioxothian-4-yl)butanamides as potent and selective dipeptidyl peptidase IV inhibitors

A series of novel 3-amino-N-(4-aryl-1,1-dioxothian-4-yl)butanamides were investigated as dipeptidyl peptidase IV (DPP-4) inhibitors. Introduction of a 4-phenylthiazol-2-yl group showed highly potent DPP-4 inhibitory activity. Among various derivatives, (3R)-3-amino-N-(4-(4-phenylthiazol-2-yl)-tetrahydro-2H-thiopyran-4-yl)-4-(2,4,5-trifluorophenyl)butanamide 1,1-dioxide (30) reduced blood glucose excursion in an oral glucose tolerance test by oral administration.     

Synthetic ColE1 plasmids carrying genes for penicillin-binding proteins in Escherichia coli

Clarke and Carbon's collection of 2000 Escherichia coli strains which harbor ColE1 plasmids carrying small random segments of the E. coli chromosome was screened for the correction of mutational defects in penicillin-binding proteins (PBPs): ponA (PBP-1a), ponB (PBP-1b), dacB (PBP-4), and pfv (PBP-5). We found plasmids carrying chromosomal segments containing ponA⁺-aroB⁺ (pLC29-47), ponB⁺-tonA⁺ (pLC4-43, pLC4-44, and pLC19-19), and argG⁺-dacB⁺ (pLC10-46 and pLC18-38). Characters of these plasmids were analyzed. Two other plasmids (pLC26-6 and pLC4-14) previously found to correct ftsI mutation (Y. Nishimura, Y. Takeda, A. Nishimura, H. Suzuki, M. Inouye, and Y. Hirota (1977)Plasmid1, 67–77) were also investigated further. Restriction maps of chromosomal DNAs carried by pLC29-47, pLC4-44, pLC19-19, pLC18-38, pLC26-6, and pLC4-14 were constructed. The regions of ponB-tonA on pLC4-44 and pLC19-19, and of leuA-ftsI-murE and F on pLC26-6 were located on the restriction maps. Although both pLC26-6 and pLC4-14 corrected a thermosensitive mutation, ftsI, which causes a defect in cell division due to abnormal PBP-3, only pLC26-6 led to restoration of PBP-3 production by an ftsI mutant, while pLC4-14 did not. Restriction and heteroduplex analyses of pLC26-6 and pLC4-14 have shown the absence of nucleotide sequence homology between them. The plasmids, pLC29-47 carrying ponA⁺ and pLC4-43, pLC4-44, and pLC19-19 carrying ponB⁺ led the host cell to overproduce the respective PBP.     

Effect of (E4, Z6)-4,6-Hexadecadienal in attraction of Stathmopoda masinissa with its pheromone components of Korean population

Timely insecticidal application for Stathmopoda masinissa Meyrick (Lepidoptera: Stathmopodidae), is important, for reducing damage to persimmon (Diospyros kaki Thunb.), an important tree fruit cultivated in Korea. In this regard, the early and precise detection of adult S. masinissa is desirable. In this study, we report the effect of (E4,Z6)-4,6-hexadecadienal (E4,Z6-16Ald) with sex pheromone components in attracting S. masinissa males. The sex pheromone of S. masinissa in the Korean population comprised two components, (E4,Z6)-4,6-hexadecadienyl acetate (E4,Z6-16Ac) and (E4,Z6)-4,6-hexadecadienol (E4,Z6-16OH). It was shown that the E4,Z6-16Ald acts as a synergist of E4,Z6-16Ac for attracting S. masinissa in the Japanese population. To test whether E4,Z6-16Ald could be used as an attractant in the Korean population, the E4,Z6-16Ald with the two pheromone components was evaluated in attracting S. masinissa males. Electroantennography (EAG) assays were performed to determine the antennal responses of S. masinissa males to the two pheromone components and E4,Z6-16Ald tested. A field attraction test with a combination of pheromones and E4,Z6-16Ald was carried out for 3 years in three different regions in Korea. E4,Z6-16Ald elicited as high a response as the two pheromone components. A mixture of the two pheromone components and E4,Z6-16Ald and a mixture of E4,Z6-16Ac and E4,Z6-16Ald attracted more S. masinissa males than a mixture of E4,Z6-16Ac and E4,Z6-16OH, the pheromone of Korean population. This new pheromone lure formulation with E4,Z6-16Ald is expected to contribute to the precise detection of S. masinissa by luring males to pheromone-baited traps.     

Oligofuro- and spiro-stanosides of Asparagus adscendens

Two oligofurostanosides and two spirostanosides, isolated from a methanol extract of Asparagus adscendens (leaves), were characterized as 3-O-[{α-l-rhamnopyranosyl (1 → 4)} {α-l-rhamnopyranosyl (1 → 6)}-β-d-glucopyranosyl]-26-O-[β-d-glucopyranosyl]-22α-methoxy-(25S)-furost-5-en-3β,26-diol (Adscendoside A), 3-O-[{α-l-rhamnopyranosyl (1 → 4)} {α-l-rhamnopyranosyl (1 → 6)}-β-d-glucopyranosyl]-26-O-[β-d-glucopyranosyl]-(25S)-furost-5-en-3β,22α,26-triol-(Adscendoside B), 3-O-[{α-l-rhamnopyranosyl (1 → 6)}-β-d-glucopyranosyl]-(25S)-spirostan-5-en-3β-ol (Adscendin A) and 3-O-[{α-l-rhamnopyranosyl (1 → 4)} {α-l-rhamnopyranosyl (1 → 6)}-β-d-glucopyr anosyl]-(25S)-spirostan-5-en-3β-ol (Adscendin B), respectively. Adscendin B and Adscendoside A are the artefacts of Adscendoside B formed through hydrolysis and methanol extraction respectively.bl]     

Identification of a novel C22-?4-producing docosahexaenoic acid (DHA) specific polyunsaturated fatty acid desaturase gene from Isochrysis galbana and its expression in Saccharomyces cerevisiae

Isochrysis galbana, produces long chain polyunsaturated fatty acids including docosahexaenoic acid (DHA, 22:6n-3). A novel gene (IgFAD4-2), encoding a C22-?4 polyunsaturated fatty acid specific desaturase, has been isolated and characterized from I. galbana. A full-length cDNA of 1,302?bp was cloned by LA-PCR technique. The IgFAD4-2 encoded a protein of 433 amino acids that shares 78?% identity with a previously reported ?4-desaturase (IgFAD4-1) from I. galbana. The function of IgFAD4-2 was deduced by its heterologous expression in Saccharomyces cerevisiae, which then desaturated docosapentaenoic acid (DPA, 22:5n-3) to DHA. The conversion ratio of DPA to DHA was 34?%, which is higher than other ?4-desaturases cloned from algae. However, IgFAD4-2 did not catalyze the desaturation or elongation reactions with other fatty acids. These results confirm that IgFAD4-2 has C22-?4-PUFAs-specific desaturase activity.     

(—)-Massoniresinol,a lignan from Pinus massoniana

A new lignan, named (—)-massoniresinol, has been isolated from Pinus massoniana needles. Its structure has been proved to be (2R,3S,4R)-3,4-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-4-(4-hydroxy-3-methoxybenzyl)-3-tetrahydrofuranmethanol by ¹H NMR, ¹³C NMR, mass and CD spectroscopy.     

Discovery of DA-1229: a potent, long acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes

A series of β-amino amide containing substituted piperazine-2-one derivatives was synthesized and evaluated as inhibitors of dipeptidyl pepdidase-4 (DPP-4) for the treatment of type 2 diabetes. As results of intensive SAR study of the series, (R)-4-[(R)-3-amino-4-(2,4,5-trifluorophenyl)-butanoyl]-3-(t-butoxymethyl)-piperazin-2-one (DA-1229) displayed potent DPP-4 inhibition pattern in several animal models, was selected for clinical development.     

Synthesis and HMG-CoA reductase inhibition of 2-cyclopropyl-4-thiophenyl-quinoline mevalonolactones

A novel series of 2-cyclopropyl-4-thiophenyl quinoline-based mevalonolactones were synthesized from the substituted anilines by several reactions. Among them, (4R,6S)-6-[(E)-2-(2-cyclopropyl-6-fluoro-4-(4-fluoro-thiophenyl)-quinoline-3-yl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (1d), (4R,6S)-6-[(E)-2-(2-cyclopropyl-6-fluoro-4-(3-methoxy-thiophenyl)-quinoline-3-yl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (1f) and (4R,6S)-6-[(E)-2-(2-cyclopropyl-6-fluoro-4,7-di(3-methoxy-thiophenyl)-quinoline-3-yl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (1q) showed potent HMG-CoA reductase inhibitory activity comparable with pitavastatin.     

Structure of orthenthose

A new tetrasaccharide, orthenthose, has been isolated from the dried twigs of Orthenthera viminea (Family: Asclepiadaceae). By spectral and chemical procedures, this new tetrasaccharide has been shown to be O-α-l-oleandropyranosyl-(1→4)-O-α-l-oleandropyranosyl-(1→4)-O-α-l-oleandropyranosyl-(1→4)-β-l-oleandropyrano se.     

Sapatoxins,aliphatic ester tigliane diterpenes from Sapium indicum

From the unripe fruits of Sapium indicum, three aliphatic esters of the tigliane nucleus were isolated. These compounds were derivatives of 4-deoxyphorbol. Sapatoxin A was identified as 12-O-[n-deca-2,4,6-trienoyl]-4-deoxyphorbol-13-acetate, B as 12-O-[n-deca-2,4,6-trienoyl]-4-deoxy-5-hydroxyphorbol-13-acetate and C as 12-O-[n-deca-2,4,6-trienoyl]-4,20-dideoxy-5-hydroxyphorbol-13-acetate, by spectroscopic analysis and hydrolysis reactions.