New azacyclopropene derivatives from Dysidea fragilis collected in Pohnpei

The sponge Dysidea fragilis from Pohnpei contained four azacyclopropene derivatives, (4E)-S-dysidazirine [2], which is the optical enantiomer of the known compound dysidazirine [1], (4Z)-dysidazirine [3], (4E)-S-antazirine [4], and (4Z)-antazirine [5]. The structures of the new compounds were elucidated by interpretation of spectral data.     

Divinyl ethers and hydroxy fatty acids from three species of Laminaria (brown algae)

Three species of brown algae, Laminaria sinclairii, L. saccharina and L. setchellii, have been investigated for the presence of oxylipins. From one, L. sinclairii, three new divinyl ether fatty acids have been characterized as methyl ester derivatives (methyl 12-[1'(Z),3'(Z)-hexadienyloxy]-6(Z), 9(Z),11(E)-dodecatrienoate, methyl 12-[1'(Z),3'(Z)-hexadienyloxy]-9(Z), 11(E)-dodecadienoate, and methyl 14-[1'(Z),3'(Z)-hexadienyloxy]- 5(Z),8(Z),11(Z),13(E)-tetradecatetraenoate) by a variety of spectroscopic methods. In addition, one new [13(S)-hydroxy-6(Z),9(Z),11(E),15(Z)-octadecatetraenoic acid] and four known monohydroxy polyunsaturated fatty acids have been isolated from all three species as their methyl ester derivatives. The occurrence of these compounds in brown algae strongly suggests that these organisms possess an active lipoxygenase(s) with omega 6 specificity.     

Disaccharide polyphosphates based upon adenophostin A activate hepatic D-myo-inositol 1,4,5-trisphosphate receptors

The glyconucleotides adenophostin A and B are the most potent known agonists at type 1 inositol trisphosphate [Ins(1,4,5)P3] receptors, although their stuctures differ markedly from that of Ins(1,4,5)P3. Equilibrium competition binding with [3H]Ins(1,4,5)P3 and unidirectional 45Ca2+ flux measurements were used to examine the effects of adenophostin A in hepatocytes, which express predominantly type 2 Ins(1,4,5)P3 receptors. Both Ins(1,4,5)P3 (Kd = 8.65 +/- 0.98 nM) and adenophostin A (Kd = 0.87 +/- 0.20 nM) bound to a single class of [3H]Ins(1,4,5)P3-binding site and each fully mobilized the same intracellular Ca2+ pool; although, adenophostin A (EC50 = 10.9 +/- 0.7 nM) was more potent than Ins(1,4,5)P3 (EC50 = 153 +/- 11 nM). Working on the assumption that it is the phosphorylated glucose component of the adenophostins that mimics the critical features of Ins(1,4,5)P3, we synthesized various phosphorylated disaccharide analogs containing this structure. The novel disaccharide-based analogs, sucrose 3,4,3'-trisphosphate [Sucr(3,4,3')P3], alpha,alpha'-trehalose 3,4,3',4'-tetrakisphosphate [Trehal(3,4,3',4')P4], alpha,alpha'-trehalose 2,4,3', 4'-tetrakisphosphate [Trehal(2,4,3',4')P4], and methyl 3-O-(alpha-d-glucopyranosyl)-beta-d-ribofuranoside 2,3', 4'-trisphosphate [Rib(2,3',4')P3], were all able to mobilize the same intracellular Ca2+ pool as Ins(1,4,5)P3 and adenophostin A; although, none was as potent as adenophostin A. The rank order of potency of the analogs, adenophostin A > Ins(1,4,5)P3 approximately Rib(2,3',4')P3 > Trehal(2,4,3',4')P4 > Glc(2',3,4)P3 approximately Trehal(3,4,3',4')P4 > Sucr(3,4,3')P3, was the same in radioligand binding and functional assays of hepatic Ins(1,4,5)P3 receptors. Both Rib(2,3',4')P3, which was as potent as Ins(1,4,5)P3, and Trehal(2,4,3',4')P4 bound with significantly higher affinity ( approximately 27 and approximately 3-fold, respectively) than the only active carbohydrate agonist of Ins(1,4,5)P3 receptors previously examined [Glc(2',3,4)P3]. We conclude that phosphorylated disaccharides provide novel means of developing high-affinity ligands of Ins(1,4,5)P3 receptors.     

Karsoside and scropolioside D, two new iridoid glycosides from Scrophularia ilwensis

Two new iridoid glycosides, karsoside [1] and scropolioside D [2], were isolated from the aerial parts of Scrophularia ilwensis. Their structures were elucidated on the basis of chemical and spectral data as 6'-O-(beta-D-xylopyranosyl)-methylcatalpol and 6-O-[(2",4"-di-O-acetyl-3"-O-trans-cinnamoyl)-alpha-L-rhamnopyranosyl]- catalpol, respectively. Additionally, four known iridoids (aucubin, harpagide, 8-O-acetylharpagide, and ajugol), a phenylpropanoid glycoside (angoroside C), and two flavonoids (quercetin-3-O-rutinoside and kaempferol-3-O-rutinoside) were isolated and identified.     

"Role of analogical reasoning in the induction of problem categories": Correction.

Reports an error in the original article by D. D. Cummins (Journal of Experimental Psychology: Learning, Memory, and Cognition, 1992[Sep], Vol 18[5], 1103–2124). On page 1111, there are labeling errors in 2 figures. In Figure 1c, problem 11 should have a "V' in the topic column; that line should read "11 V Fl.' In Figure 1d, problems 2 and 4 should have "CU' in the structure column; those lines should read "2 T CU' and "4 T CU,' respectively. Also in that figure, problems number 8 and 13 should have "Fl' in the structure column; those lines should read "8 V Fl' and "13 W Fl.' (The following abstract of this article originally appeared in record 1993-04297-001.) In 3 experiments, novices were required to answer questions while reading a series of problems. The questions required them either to analyze individual problem structures (intraproblem processing) or compare problem structures (analogical comparison processing) to derive answers … (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Metabolism of daidzein and genistein by intestinal bacteria

The isoflavones daidzein [1] and genistein [2] were fermented with human fecal bacteria under anaerobic conditions. Dihydrodaidzein [3], benzopyran-4,7-diol,3-(4-hydroxyphenyl) [4], and equol [5] were isolated from the fermentation broth of 1. Only one metabolite, dihydrogenistein [6], was isolated and characterized from the fermentation broth of 2. Metabolites 3-6 were identified by spectral methods.     

Z-->B transition in poly[d(G-m5C)2] induced by interaction with 4',6-diamidino-2-phenylindole

The Z form of poly[d(G-m5C)2], in presence of Mg2+ ion, is found to be transformed into B form upon interaction with 4',6-diamidino-2-phenylindole (DAPI). The Z-->B transformation is complete at a mixing ratio of about 0.07 DAPI per DNA base pairs, i.e., each DAPI molecule may be related to the conversion of 6-7 base pairs. An interaction between DAPI and poly[d(G-m5C)2] in its Z form at low drug: DNA ratios is suggested from optical dichroism and time-resolved luminescence anisotropy results. The spectroscopic behaviour of DAPI indicates that the Z conformation of DNA does not provide normal binding sites for DAPI, such as groove or intercalation sites, but that the initial association may be of external nature.     

Examination of the degree of agreement among dental findings used for personal identification (report 5)--canonical correlation between dental findings on dental charts and those on radiographs

Findings obtained from dental charts and from radiograph taken one year later for the same individuals were examined and classified according to different criteria. Similarities between the two sources investigated by the canonical correlation method. The results obtained were as follows: 1. The correlation coefficient and the squared multiple correlations (R2) were calculated. Consequently, high similarities were seen between the two sources for the mandibular anterior teeth [sequence: see text], maxillary incisor teeth [sequence: see text], mandibular and maxillary first premolar teeth [sequence: see text], and the corresponding teeth of the same jaws. 2. Three roots showed high elucidative values by the canonical correlation method. The first root was understood to be the mandibular incisor factor, the second the maxillary incisor factor, and the third the first premolar factor. This seemed to indicate, that the similarities between the two sources in these regions were very high. 3. A study of the similarities between the two sources was done based on the individual scores of canonical variable loadings calculated in this analysis. High similarities were seen at [sequence: see text] in category 1 (intact & C1) for chart findings and category 1'(intact, C1-C3 & resin filling) for radiographic findings: at [sequence: see text] in category 2 (C2-C4, inlay & filling of repair) for chart findings and category 3'(stump of tooth) for radiographic findings; and at [sequence: see text] in category 3 (complete crown, jacket crown & post crown) for chart findings and category 3'(stump of tooth) for radiographic findings. 4. The present results suggest that if proper case in taken, one set of information can serve as a substitute for the other. In personal identification, higher efficiency may be achieved if this is borne in mind.     

Letter to The Editor, Canadian Psychologist: Dear Mr. Gibson.

In this letter to the editor, O. Spreen reports an error in "Applied Training Programmes of Psychology in Canada: A Survey" by Artur Z. Arthur (Canadian Psychologist Psychologie Canadienne, 1971[Jan], Vol 12[1], 46-65). Page 49 contains an error regarding the available staff for applied training programs at the University of Victoria. The correct figure under column 7 (staff, full-time, psychology) should not be 40. Instead the correct figure for 1971-72 should be 11; under "staff, other departments", 4 should be listed; under "staff, part-time", 1 should be listed; under "staff in applied settings", 3 should be listed. (The following abstract of the original article appeared in record 2007-02140-007.) A survey of professional applied training programmes in the Canadian universities was carried out in 1969. Reported were 29 programmes: 17 in clinical psychology, 4 each in counselling and school psychology, one each in educational psychology and learning disabilities and 2 in experimental psychopathology. The number of places in the universities was related to the expected manpower requirements. Information was also given concerning the numbers of teachers in each programme, the types of applied settings utilized, and the different courses offered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Studies on the constituents of Calliandra anomala (Kunth) Macbr. I. Structure elucidation of two acylated triterpenoidal saponins

Two novel triterpenoidal saponins, called calliandra saponins A and E, were isolated from the branches of Calliandra anomala (Kunth) Macbr. On the basis of the chemical and physiocochemical evidence, their structures were defined as 3-O-alpha-L-arabinopyranosyl-(1-->2)-alpha-L-arabinopyranosyl++ +-(1-->6)-2- acetamido-2-deoxy-beta-D-glucopyranosyl echinocystic acid 28-O-(beta-D-glucopyranosyl-(1-->3)-[beta-D-xylopyranosyl-(1-->3)-beta-D - xylopyranosyl-(1-->4)]-alpha-L-rhamnopyranosyl-(1-->2)-[(6S)-2-trans- 2,6-dimethyl-6-O-beta-D-xylopyranosyl-2,7-octadienoyl-(1-->6)]-bet a-D- glucopyranosyl) ester (4) and 3-O-alpha-L-arabinopyranosyl-(1-->2)-alpha-L-arabinopyranosyl++ +-(1-->6)-2- acetamido-2-deoxy-beta-D-glucopyranosyl echinocystic acid 28-O-[beta-D-glucopyranosyl-(1-->3)-[beta-D-xylopyranosyl-(1-->3)-beta-D - xylopyranosyl-(1-->4)]-alpha-L-rhamnopyranosyl-(1-->2)-[(6'S)-2'-trans- 2',6'-dimethyl-6'-O-(2-O-(6S)-2-trans-2,6-dimethyl-6-hydroxy-2,7-octa dienoyl)- beta-D-xylopyranosyl-2',7'-octadienoyl-(1-->6)]-beta-D-glucopyr ano syl] ester (5), respectively.     

In vitro biosynthesis of a decasaccharide prototype of multiply branched polylactosaminoglycan backbones

Multiply branched polylactosaminoglycans are expressed in glycoproteins and glycolipids of many cells. Interest in their biology stems from their abundant expression in early embryonal cells and from their ability to carry multiple lectin-binding determinants, which makes them prominent ligands and antagonists of cell adhesion proteins. A prototype of their backbones is represented by the decasaccharide LacNAc beta1-3'(LacNAc beta1-6')LacNAc beta1-3'(LacNAc beta1-6')LacNAc (5), where LacNAc is the disaccharide Gal beta1-4GlcNAc. Here, we describe in vitro biosynthesis of glycan 5. Incubation of the linear hexasaccharide LacNAc beta1-3'LacNAc beta1-3'LacNAc (1) with UDP-GlcNAc and alpha midchain beta1,6-GlcNAc transferase activity (GlcNAc to Gal), present in rat serum [Gu, J., Nishikawa, A., Fujii, S., Gasa, S., & Taniguchi, N. (1992) J. Biol. Chem. 267, 2994-2999], gave the doubly branched octasaccharide LacNAc beta1-3'(GlcNAc beta1-6')LacNAc beta1-3'(GlcNAc beta1-6')LacNAc (4). The latter was converted to 5 by enzymatic beta1,4-galactosylation. In the initial branching reaction of 1, two isomeric heptasaccharide intermediates, LacNAc beta1-3'LacNAc beta1-3'(GlcNAc beta1-6')LacNAc (2) and LacNAc beta1-3'(GlcNAc beta1-6')LacNAc beta1-3'LacNAc (3), were formed first at comparable rates. Later, both intermediates were converted to 4, revealing two distinct pathways of the reaction: 1 --> 2 --> 4 and 1 --> 3 --> 4. These data suggest that, regardless of their chain length, linear polylactosamines similar to 1 contain potential branching sites at each of the internal galactoses. The enzyme-binding epitope of 1 is probably LacNAc beta1-3'LacNAc, because the trisaccharides GlcNAc beta1-3'LacNAc and LacNAc beta1-3Gal as well as the tetrasaccharide GlcNAc beta1-3'LacNAc beta1-3Gal were poor acceptors, while LacNAc beta1-3'LacNAc was a good one. Midchain beta1,6-GlcNAc transferase activities present in serum of several mammalian species, including man, resembled closely the rat serum activity in their mode of action and in their acceptor specificity. We suggest that analogous membrane-bound Golgi enzymes are involved in the biosynthesis of multiply branched polylactosamines in vivo.     

Orally active cephalosporins. II. Synthesis and structure-activity relationships of new 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-cephalospori ns with 1,2,3-triazole in C-3 side chain

The synthesis, antibacterial activity and oral absorbability of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3 -(1H-1,2, 3-triazol-4-yl)thiomethylthio-3-cephem-4-carboxylic acid (1g) and related compounds are described. Their oral absorbability was influenced by the spacer length between C-3 of a cephem nucleus and C-4' of 1,2,3-triazole. The SCH2S structure was also found to contribute to their good oral absorption. The quantitative relationship between the bioavailability and the spacer length of cephalosporins (1a-1n) is discussed.     

Kienb?ck''s disease. II. Risk factors, diagnosis, and ergonomic interventions

1. Biotransformation of warfarin by the fungus Beauveria bassiana (ATCC 7159) yielded the first reported phase II warfarin metabolite, 3'4'-dihydroxywarfarin-3'-[4-methoxyglucoside], another previously unreported metabolite, 3',4'-dihydroxywarfarin and also 4'-hydroxywarfarin. 2. Biotransformation of warfarin by Streptomyces rimosus (NRRL 2234) yielded the previously unreported metabolites, 12-hydroxywarfarin, 4'-hydroxy-11-methoxywarfarin, and also 7-hydroxywarfarin and 4'-hydroxywarfarin, which have not been previously reported as biotransformation products from this organism. 3. Hplc-nmr has been used to identify biotransformation products of warfarin by S. rimosus directly from the microbial broth without prior isolation and purification.     

Effects of gavage versus dosed feed administration on the toxicokinetics of benzyl acetate in rats and mice

8-epi-prostaglandin F2 alpha stimulated contraction of human myometrial strips obtained from five different donors at the time of hysterectomy with a pEC50 value of 6.3 +/- 0.5. In paired strips from the same donors the pEC50 value for the selective TP receptor agonist U46619 ([1R-[1a,4a,5b(Z),6a(1E,3S*)]]-7-[6-(3- hydroxy-1-octenyl)-2-oxabicyclo[2.2.1]hept-5-yl]-5-heptenoic acid) was 8.3 +/- 0.4. In strips from four other donors 8-epi-prostaglandin F2 alpha was ineffective whereas the pEC50 for U46619 was 6.9 +/- 0.3. Responses to 8-epi-prostaglandin F2 alpha were unaffected by the selective DP receptor antagonist BW A868C (3-benzyl-5-(6-carboxyhexyl)-1-(2- cyclohexyl-2-hydroxyethylamino)hydantoin) at 50 nM but were blocked by the selective TP receptor antagonist L670596 ((-)6,8-difluoro-9-p-methylsulfonyl benzyl-1,2,3,4- tetrahydrocarbazol-1-yl-acetic acid) at 50 nM. The pIC50 values obtained when the TP receptor antagonists GR 32191 ([1R- [1 alpha(Z),2 beta,3 beta,5 alpha]]-(+)-7-[5-[[(1,1'-biphenyl)-4- yl]methoxy]-3-hydroxy-2-(1-piperidinyl)cyclopentyl]-4-heptenoic acid), ICI D1542 ((4(Z)-6-[(2S,4S,5R)-2-[1-methyl-1-(2-nitro-4-tolyloxy)ethyl]- 4-(3-pyridyl)-1,3-dioxan-5-yl]hex-4-enoic acid), ICI 192605 (4(Z)-6-[(2,4,5-cis)-2-(2-chlorophenyl)-4-(2-hydroxyphenyl)-1,3- dioxan-5-yl]hexenoic acid), L670596 and SQ 29548 ([1S-(1 alpha,2 beta(5Z),3 beta,4 alpha]]-7- [3-[[2-[(phenylamino)carbonyl]hydrazino]methyl]-7- oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid) were added cumulatively to strips pre-contracted with an EC80 concentration of 8-epi-prostaglandin F2 alpha were not significantly different from those obtained when an EC80 concentration of U46619 was used. The effects of 8-epi-prostaglandin F2 alpha on strips pre-contracted with an EC80 concentration of U46619 were not different from those of U46619 itself. It is concluded that in the non-pregnant human myometrium 8-epi-prostaglandin F2 alpha is a medium potency contractile agonist acting predominantly at the TP receptor.     

Structural studies by high-field NMR spectroscopy of a binary-addressed complementary oligonucleotide system juxtaposing pyrene and perfluoro-azide units

Recently, a new approach has been proposed to improve the site-specificity and efficiency of the modification of nucleic acid target sequences, the binary system of complementary-addressing nucleic acid sequences. The binary system comprises two oligonucleotides, one modified with a photosensitizing group and the other with a photoreactive group. The sites of chemical modification are arranged to bring the two chemical functions close enough together in space to allow efficient energy transfer from the photo-excited photosensitizer to an arylazide moiety which expels N2 to form a nitrene which subsequently covalently labels the target nucleic acid. Structural analysis performed by high-resolution 2D NMR spectroscopy (400 MHz and 600 MHz) are reported for the model binary system 1:2:3, where 1 is the target 12-mer pdGTATCAGTTTCT, 2 is a photoactivatable fluoroazide derivative dAGAAACp-L-Az and 3 is the photosensitizer derivative Pyr-pdTGATAC (here: Az is the p-azidotetrafluorobenzyl group, Pyr the pyrenyl-1-methylamino group, L a linker group). The assignment of oligonucleotide and modifying group protons was performed using 1H COSY, TOCSY and NOESY experiments. Comprehensive analysis of 1H NOESY spectra of 1:2:3 showed that terminal fragments of the complex [5'p-1T-2G-3A-4T-], [-21A-22T-23A-24C], [-8T-9T-10T-11C-12T] and [13A-14G-15A-15A-17A-18C-] gave a continuous set of intra- and inter-nucleotide interactions, typical of regular double-stranded B-DNA. In contrast, the central region of the complex composed of 5C, 6A, 7G, 19T and 20G nucleotide residues, nearest the Pyr and Az groups, was found to be distorted. Thus some signals from aromatic and/or sugar-ring protons of the above nucleotide residues were extremely broadened or almost absent. Moreover, some intra- and/or inter-nucleotide interactions, typical of the regular DNA duplex, were not detected for the [-5C-6A-7G-] and [-19T-20G-] regions of the tandem system. Instead of that, some cross-peaks of low-intensity between the H2 proton of the Pyr group and 7G(H1'), 7G(H2'/H2"), 7G(H3'), 4T(H2"), 4T(H4') and 4T(H5'/H5") were observed. Additional 1H -1H NOE-interactions between methylene protons of the linker group L and some sugar ring protons of 18C nucleotide residue were detected. A preliminary structural model, constructed using proton-proton distances between Pyr and the DNA and Az-L and DNA obtained from a 1H NOESY experiment at 300 ms mixing time as constraints for the refinement of the structure, displayed significant distortion from B-DNA of the double-stranded helix in the middle of the complex, (-5C-6A-7G, -18C-19T-20G-). The Pyr group was located in what remains of the minor groove near 4T, 5C, 6A and 7G and the centroid of the azide ring less than 9A degrees from the centroid of the ring system of Pyr group.     

"The experience of "forgetting" childhood abuse: A national survey of psychologists": Correction.

Reports 2 errors in the Results section of the original article by S. Feldman-Summers and K. S. Pope (Journal of Consulting and Clinical Psychology, 1994[June], Vol 62[3], 636–639). The 1st sentence of paragraph 2 in the subsection Reported Abuse should read, "Sexual abuse was reported by 22.7% of the women and by 16.5% of the men, for a total of 20% of the sample.' A correction is also provided for the final sentence of paragraph 3 in the subsection Forgotten Abuse. (The following abstract of this article originally appeared in record 1994-39093-001.) A national sample of psychologists were asked whether they had been abused as children and, if so, whether they had ever forgotten some or all of the abuse. Almost a quarter of the sample (23.9%) reported childhood abuse, and of those, approximately 40% reported a period of forgetting some or all of the abuse. The major findings were that (1) both sexual and nonsexual abuse were subject to periods of forgetting; (2) the most frequently reported factor related to recall was being in therapy; (3) approximately one half of those who reported forgetting also reported corroboration of the abuse; and (4) reported forgetting was not related to gender or age of the respondent but was related to severity of abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A pathway for biosynthesis of divinyl ether fatty acids in green leaves

[1-14C]alpha-Linolenic acid was incubated with a particulate fraction of homogenate of leaves of the meadow buttercup (Ranunculus acris L.). The main product was a divinyl ether fatty acid, which was identified as 12-[1'(Z),3'(Z)-hexadienyloxy]-9(Z),11(E)-dodecadienoic acid. Addition of glutathione peroxidase and reduced glutathione to incubations of alpha-linolenic acid almost completely suppressed formation of the divinyl ether acid and resulted in the appearance of 13(S)-hydroxy-9(Z), 11(E),15(Z)-octadecatrienoic acid as the main product. This result, together with the finding that 13(S)-hydroperoxy-9(Z), 11(E),15(Z)-octadecatrienoic acid served as an efficient precursor of the divinyl ether fatty acid, indicated that divinyl ether biosynthesis in leaves of R. acris occurred by a two-step pathway involving an omega6-lipoxygenase and a divinyl ether synthase. Incubations of isomeric hydroperoxides derived from alpha-linolenic and linoleic acids with the enzyme preparation from R. acris showed that 13(S)-hydroperoxy-9(Z),11(E)-octadecadienoic acid was transformed into the divinyl ether 12-[1'(Z)-hexenyloxy]-9(Z), 11(E)-dodecadienoic acid. In contrast, neither the 9(S)-hydroperoxides of linoleic or alpha-linolenic acids nor the 13(R)-hydroperoxide of alpha-linolenic acid served as precursors of divinyl ethers.     

Novel pyrimidinediones and thiazolidinones as anti depressants

2-Mercapto-5-[4'-methoxy phenyl thiourea]-1,3,4-thiadiazole (2a-c) prepared by the condensation of 2-amino-5-mercapto-1,3,4-thiadiazole (1) with substituted phenyl isothiocyanates. Further on cyclisation with malonic acid in the presence of acetyl chloride gave the corresponding 2-mercapto-5-[3-(4-methoxy phenyl)-2-thioxo-2-5-dihydro-4, 6-pyrimidionoyl]-1,3,4-thiadiazole (3a-c) [sequence: see text]. This on further reaction with substituted aryl aldehydes in presence of zinc chloride gave 2-mercapto-5-[3-(4'-methoxy phenyl)-2'-thioxo-2',5'-dihydro-4',6' -pyrimidionoyl 5'-phenyl carboxaldehyde]-1,3,4- thiadiazole (4a-g) [sequence: see text]. The compounds were screened for antidepressant activity and compared with antidepressant (imipramine).     

Synthesis and structure-activity relationships of cephalosporins, 2-isocephems, and 2-oxaisocephems with C-3' or C-7 catechol or related aromatics

A series of cephalosporins, 2-isocephems, and 2-oxaisocephems with C-3' catechol-containing (pyridinium-4-thio)methyl groups and 2-isocephems with C-7 catechol related aromatics have been prepared and evaluated for antimicrobial activity. It turns out that these compounds have highly potent activity against Gram-negative bacteria, especially resistant pathogens such as Pseudomonas aeruginosa. The most active compound of the series was (6S,7S)-7-[2-(2-aminothiazol-4-yl)-2-[(Z)-[(1,5-dihydroxy-4-pyr idon-2-yl) methoxy]imino]acetamido]-3-[[[(4-methyl-5-carboxymethyl)thiazol-2- yl] thio]methyl]-8-oxo-1-aza-4-thiabicyclo [4.2.0] oct-2-ene-2-carboxylic acid which exhibited potent in vitro activity against clinically isolated P, aeruginosa and Acinetobacter baumanii which is also resistant to many anti-infectives, and good in vivo efficacy against clinically isolated P aeruginosa.     

In vitro cross-resistance and collateral sensitivity in seven resistant small-cell lung cancer cell lines: preclinical identification of suitable drug partners to taxotere, taxol, topotecan and gemcitabin

The thiazole orange dye 1,1'-(4,4,8,8-tetramethyl-4,8-diazaundecamethylene)-bis[4-[3-methy l-2, 3-dihydro(benzo-1,3-thiazole)-2-methylidene]]quinolinium tetraiodide (TOTO) binds to double-stranded DNA (dsDNA) in a sequence selective bisintercalation. Each chromophore is sandwiched between two base pairs in a (5'-CpT-3'):(5'-ApG-3') site, and the linker spans over two base pairs in the minor groove. The binding of analogs of TOTO in which the linker has been modified is examined. The aim of the study is to utilize the sequence selectivity of the TOTO chromophores to enhance and/or alter the overall selectivity of the binding. One- and two-dimensional 1H-NMR investigations of complexes between TOTO analogs and various dsDNA oligonucleotides are reported. The following analogs were synthesized and used: 1,1'-(4,4,8,8-tetramethyl-4,8-diazadodecamethylene) -bis[4-[3-methyl-2,3-dihydro- (benzo-1,3-thiazole)-2-methylidene]]quinolinium tetraiodide (TOTO10), 1,1'-(5,5,9,9-tetramethyl-5,9-diazatridecamethylene)-bis[4-[3-meth yl-2, 3-dihydro(benzo-1,3-thiazole)-2-methylidene]]quinolinium tetraiodide (TOTO11), and 1,1'-(6,6,10,10-tetramethyl-6,10-diazapentadecamethylene)-bis[4-[3 -methyl-2, 3-dihydro(benzo-1,3-thiazole)-2-methylidene]]quinolinium tetraiodide (TOTO13). The results show that with a longer linker the dyes can bisintercalate into two (5'-CpT-3'):(5'-ApG-3') sites separated by one or two base pairs. Bisintercalation in two such "isolated" binding sites yields non-nearest-neighbor bisintercalation in which the linker spans over more than two base pairs. The investigations also showed that an exact length of the linker is not crucial for the site selectivity since TOTO, TOTO10, and TOTO11 are almost equally suitable in binding selectively to the (5'CTAG-3')2 sequence. Fluorescence measurements show that TOTO10, TOTO11, and TOTO13 have higher fluorescence quantum yields than TOTO when bound to d(CGCTAGCG)2. This indicates that the length of the linker in TOTO may not be the optimum one in terms of using the dye as a fluorescence marker.