Photocatalytic and free radical interactions of the heterocyclic N-oxide resazurin with NADH, GSH, and Dopa

Electron donating free radicals NAD(.), (.)CO2(-), MV(.)+, and e(aq)-, generated by pulse radiolysis, reduce resazurin (RNO) with rate constants of 1.9 x 10(9), 2.8 x 10(9), 4.8 x 10(9), and 2.3 x 10(10) M(-1) s(-1), respectively, neutral solution. The semireduced dye (RN(.)-O- disproportionates slowly to RN (resorufin) and RNO. There was little evidence that RN(.)-O- behaves as an oxidizing species capable of initiating chain reactions, for instance via oxidation of NADH to NAD(.). The oxidizing radicals GS(.), (.)OH, and N3(.) interact with RNO via complex consecutive processes, probably by addition-elimination reactions. Stable products generated upon oxidation of RNO by N3(.) exhibit a red-shifted absorption, but GS(.) and (.)OH also cause partial reduction to RN. Neither O2(.)- nor dopa semiquinone nor tyrosine phenoxyl radicals appear to interact with RNO. Radicals formed by reaction of (.)OH with (Gly)3 reduce RNO to RN with stoichiometry near two (gamma-radiolysis), and there is evidence (pulse radiolysis) for direct slow O-atom transfer from RNO to these species. Resazurin is highly photosensitive under anaerobic conditions in presence of H-atom donors like NADH, GSH, or dopa. Under aerobic conditions RNO becomes an efficient catalyst of red light induced photooxidation of these donors; the RN(.)-O- intermediate, formed in the photooxidative process, is apparently recycled to RNO by O2, and by other electron acceptors. Our results suggest that RNO can behave as a photoactive, free radical generating xenobiotic compound.     

Antifeedant activity of some new heterocyclic compounds against the larvae of Spodoptera litura F

The antifeedant activity of diisoflavones a synthetic products is reported for the first time against S. litura. The antifeedant activity was tested employing the non-choice test method against the 4th instar pre-starved larvae.     

Structural studies of the melibiose permease of Escherichia coli by fluorescence resonance energy transfer. II. Identification of the tryptophan residues acting as energy donors

In the accompanying paper, we demonstrated the presence of a fluorescence resonance energy transfer (FRET) between the tryptophans of the melibiose permease (MelB) of Escherichia coli and a fluorescent sugar, 2'-(N-5-dimethylaminonaphthalene-1-sulfonyl)aminoethyl-1-thio-beta-D- galactopyranoside (Dns2-S-Gal) bound at the sugar-binding site (Maehrel, C., Cordat, E., Mus-Veteau, I., and Leblanc, G. (1998) J. Biol. Chem. 273, 33192-33197). To identify the tryptophans that transfer their energy to the fluorescent sugar, we analyzed the FRET properties of MelB mutants carrying the replacement of each of the eight MelB tryptophans by a phenylalanine. The data indicate that Trp64, localized in loop 2-3 from the N-terminal domain, and Trp299, localized in helix IX in the C-terminal domain, are responsible for up to 80% of the FRET signal. Moreover, by assuming that only Trp299 transfers energy to Dns2-S-Gal in mutant W64F, whereas only Trp64 transfers energy to Dns2-S-Gal in mutant W299F, we calculated that Trp299 and Trp64 are about 14 and 20 A away from the probe, respectively. In addition, we observed that mutating Trp342, localized in helix X of the C-terminal domain, produces a significant increase of the polarity of the fluorescent sugar environment, suggesting its proximity to the sugar-binding site. Taken together, these data provide additional support for the suggestion that (i) the sugar-binding site is localized in the C-terminal part of the transporter, probably close to membrane segments IX and X, and (ii) the N-terminal domain, and particularly cytoplasmic loop 2-3, is also close to the sugar-binding site.     

Condensed heterocyclic compounds: synthesis and antiinflammatory activity of novel thiazolo[3,2-alpha] pyrimidines

In this study, thirty six new 2-benzylidene-7-methyl-3-oxo-5- phenyl-2,3-dihydro-5H-thiazolo[3,2-alpha]pyrimidine-6-carboxylic acid methyl esters were synthesized and characterized by spectral, crystallographic, and elemental analysis. The antiinflammatory activity of the compounds was tested by the carrageenan hind paw edema test. It was found that compound 6a having a 2-meth-oxyphenyl group at position 5 and a benzylidene group at position 2 was the most potent compound in this series. All the compounds that were tested for ulcer activity gave positive results.     

Locomotor activity responses to ethanol, other alcohols and GABA-A acting compounds in forward- and reverse-selected FAST and SLOW mouse lines.

Mice selectively bred for high (FAST) or low (SLOW) locomotor stimulant response to ethanol have been found to differ in response to drugs with gamma-aminobutyric acid (GABA)-ergic actions. Reverse selection produced lines that are similar in sensitivity to ethanol stimulation (r-FAST and r-SLOW) and provided a unique model for testing hypotheses about shared genetic influence on sensitivity to ethanol and GABAergic drugs. FAST mice were more stimulated than SLOW mice by all drugs tested: ethanol, methanol, n-propanol, t-butanol, pentobarbital, diazepam, and allopregnanolone. In contrast, r-FAST and r-SLOW mice differed in sensitivity to only a few isolated drug doses. Locomotor responses of each reverse-selected line were significantly different from the responses of their respective forward-selected line for all drugs. Results support an effect of selection for ethanol sensitivity on allosteric modulation of the GABA-A receptor. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Shape-dependent effects in a series of aromatic nitro compounds acting as mutagenic agents on S. typhimurium TA98

Freshly isolated hepatocytes of the clawed toad, Xenopus laevis, were cultured for at least 3 days. The viability of the cells was characterized using staining and biochemical methods. In particular, the glucose and glycogen balance was tested. After culture for 16-20 hrs, the cells were subjected to hormonal treatment. Both adrenaline and arginine vasotocin stimulated the release of glucose in a dose dependent manner. 10(-6) M concentrations were strongly effective. The determination of the glycogen balance made it clear that the glucose release is mainly due to glycogenolysis. Using receptor antagonists and agonists, it has been shown that the effect of adrenaline is clearly mediated by beta-type receptors. Arginine vasotocin stimulated glycogenolysis via a type of receptor which is similar to the V2-receptor of mammals. This means that cAMP is involved in the response to both types of hormones which is in contrast to that which is known about the effect of nonapeptides on the liver of mammals.     

Research on heterocyclic compounds, Part 40. 2-Phenylimidazo[1,2-a]pyridine-3-carboxylic acid derivatives: synthesis and antiinflammatory activity

A series of 2-phenylimidazo[1,2-a]pyridine-3-carboxylic esters, acids, and amides were synthesized and pharmacologically tested in order to evaluate their antiinflammatory and analgesic activity and their ulcerogenic action on the gastro-intestinal tract. The most active member of this series of compounds was found to be 6-methyl-2-phenylimidazo[1,2-a]pyridine-3-carboxylic acid (5c).     

Synthesis of benzanilide derivatives as dual acting agents with alpha 1-adrenoceptor antagonistic action and steroid 5-alpha reductase inhibitory activity

Synthesis of benzanilide derivatives which have dual alpha 1-adrenoceptor antagonistic action and steroid 5 alpha-reductase inhibitory activity and their structure-activity relationships is described.     

Polyanion inhibitors of HIV and other viruses. 7. Polyanionic compounds and polyzwitterionic compounds derived from cyclodextrins as inhibitors of HIV transmission

New polyanionic compounds were obtained from radical addition of thiomalic acid and mercaptopropionic acid onto perallylated cyclodextrins (CDs) under UV irradiation with a catalytic amount of alpha,alpha'-azobis(isobutyronitrile). All these polyanions, bearing 18-48 carboxylate groups, inhibited human immunodeficiency virus type 1 (HIV-1) strain IIIB replication in MT-4 cells at a 50% inhibitory concentration (IC50) of 0.1-2.9 microM, while not being toxic to the host cells at concentrations up to 62 microM. These compounds were also active against a clinical HIV-1 isolate (HE) at >/=4-fold higher concentrations. Only some compounds showed activity against the two HIV-2 strains (ROD and EHO) but at higher concentrations than those required to inhibit HIV-1 (IIIB and HE) replication. In addition, these compounds were not active against the M-tropic HIV-1 strain BaL but were active against simian immunodeficiency virus [SIV (MAC251)]. These compounds were also inhibitory to the replication of human cytomegalovirus at an IC50 of 1-10 microM, but not herpes simplex virus (type 1 and type 2) or other (picorna-, toga-, reo-, orthomyxo-, paramyxo-, bunya-, rhabdo-, and poxvirus) viruses. Radical addition on perallylated CDs of a protected cysteine gave polyzwitterionic compounds. None of these last compounds proved inhibitory to the replication of HIV-1, HIV-2, or any of the other viruses tested.     

Model compounds in elucidating the structural basis of HIV retrovirus activity. Synthesis of trisodium O-monoalkyl- and O-monoaryldiphosphates

OBJECTIVE: To analyse the change of blood pressure and endothelin in sleep apnea syndrome. METHODS: The ambulatory blood pressure, echocardiogram and plasma endothelin in 164 cases of hypertension and normal controls with or without sleep apnea syndrome (SAS) were examined. The patients were divided into four groups and 41 cases were in each group. RESULTS: The results showed that in a number of the patients of sleep apnea with or without hypertension blood pressure day nocturnal rhythm disappeared and endothelin increased (18.2 +/- 5.7 ng/L and 13.2 +/- 4.4 ng/L) The difference of nocturnal blood pressure and endothelin between SAS groups and non-SAS groups (11.7 +/- 3.9 ng/L and 4.3 +/- 2.1 ng/L) were statistically significant (P < 0.05 and P < 0.01). CONCLUSION: It was suggested that the SAS patients might be due to cyclical hypoxemia and nerve-endocrine abnormality activating endothelin, and other vasoactive peptides with increased blood pressure during sleep and enhance the damage to target organs.     

Activity of glutathione-dependent enzymes in long term diabetes. II. Glutathione contents and activity of glutathione-dependent enzymes: S-transferase and peroxidase in the kidney cytosol of alloxan induced diabetic rats

To better understand the uptake of oligonucleotides into cells, we have studied the labeling of cell surface proteins by an oligonucleotide conjugated to a radiolabeled photoactivatable crosslinker (Denny-Jaffe reagent). When HL60 cells are treated with the conjugate for 2 hours in a medium containing bovine serum albumin (BSA), almost all of the cell-associated label is found in one protein, which we identify as BSA. Cells grown and treated in a serum-free medium do not show this protein, whereas it is plainly seen in cells that are grown in serum-containing medium but then treated in serum-free medium. Overall association of the oligonucleotide with cells is much higher in serum-free medium than in BSA-containing medium, but the oligonucleotide is mostly not protein-associated in the absence of BSA. We conclude that (1) BSA from the medium serves to block overall association of oligonucleotide with cells, and (2) BSA is the main cell surface protein binding oligonucleotides. We discuss the possible role of albumin in endocytic uptake of oligonucleotides in the cell and in the biodistribution of oligonucleotides in vivo.