Synthesis of Acyclo C-Nucleosides OF Phenanthro[9,10-e][1,2,4]Triazino[3,4-c]-[1,2,4] Triazoles,and Their Precursors

ABSTRACT

Reaction of 3-hydrazinophenanthro[9,10-e][1,2,4]triazine (1) with aliphatic and aromatic aldehydes as well as monosaccharides gave the corresponding hydrazones 2a-g. The D-glucose analogue exists in the cyclic pyranosyl structure 5. Acetylation and partial acetylation of the sugar hydrazones were carried out. Cyclization of a number of hydrazones including the partially acetylated sugar hydrazones by thionyl chloride gave regioselectively the respective angular isomer 1-substituted phenanthro[9,10-e][1,2,4]triazino[3,4-c][1,2,4]triazoles 16i-I, and not the linear isomer. The cyclization of 1 with acetic acid, however, gave regioselectively the linear isomer 19. The structural assignments were based on a model study whereby the angular 16a was found to be different from the linear isomer 19a obtained by the condensation of 4,5-diamino-3-methyl-1,2,4-triazole with 9,10-phenanthraquinone. Periodate oxidation of 2d gave 20 whose reaction with 1 gave 21.     

Exploiting codon usage identifies intensity-specific modifiers of Ras/MAPK signaling in vivo

Signal transduction pathways are intricately fine-tuned to accomplish diverse biological processes. An example is the conserved Ras/mitogen-activated-protein-kinase (MAPK) pathway, which exhibits context-dependent signaling output dynamics and regulation. Here, by altering codon usage as a novel platform to control signaling output, we screened the Drosophila genome for modifiers specific to either weak or strong Ras-driven eye phenotypes. Our screen enriched for regions of the genome not previously connected with Ras phenotypic modification. We mapped the underlying gene from one modifier to the ribosomal gene RpS21. In multiple contexts, we show that RpS21 preferentially influences weak Ras/MAPK signaling outputs. These data show that codon usage manipulation can identify new, output-specific signaling regulators, and identify RpS21 as an in vivo Ras/MAPK phenotypic regulator.     

DFT studies of acrolein molecule adsorption on pristine and Al- doped graphenes

The ability of pristine graphene (PG) and Al-doped graphene (AlG) to detect toxic acrolein (C₃H₄O) was investigated by using density functional calculations. It was found that C₃H₄O molecule can be adsorbed on the PG and AlG with adsorption energies about ?50.43 and – v30.92 kcal mol^?1 corresponding to the most stable configurations, respectively. Despite the fact that interaction of C₃H₄O has no obvious effects on the of electronic properties of PG, the interaction between C₃H₄O and AlG can induce significant changes in the HOMO/LUMO energy gap of the sheet, altering its electrical conductivity which is beneficial to sensor designing. Thus, the AlG may be sensitive in the presence of C₃H₄O molecule and might be used in its sensor devices. Also, applying an external electric filed in an appropriate orientation (almost stronger than 0.01 a.u.) can energetically facilitate the adsorption of C₃H₄O molecule on the AlG.     

Allocentric representation in the human amygdala and ventral visual stream

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Protective effect of resveratrol against doxorubicin-induced cardiac toxicity and fibrosis in male experimental rats

The possible effectiveness of resveratrol, a polyphenol present in different plants comprising berries, grapes and peanuts, on the prevention of doxorubicin-induced cardiac toxicity and fibrosis was investigated. Forty adult male Wistar albino rats were divided into four groups. Group I received normal saline, group II gavaged with resveratrol (20 mg/kg, daily for 4 weeks), group III received doxorubicin (2.5 mg/kg i.p. in six injections for 2 weeks; accumulative dose of 15 mg/kg), and group IV received doxorubicin?+?resveratrol (starting resveratrol intake 2 weeks before doxorubicin administration). Resveratrol significantly alleviated the increase in left ventricular lipid peroxidation, hydroxyproline, and tumor necrosis factor alpha levels as well as serum creatine kinase-myocardial band (CK-MB) activity and prevented the decrease in body and heart weights in doxorubicin-treated group. However, a marked protection against reduced glutathione content depletion and superoxide dismutase activity reduction was observed in the left ventricles of rats pretreated with resveratrol in combination with doxorubicin. Resveratrol also ameliorated the up-regulation of left ventricular caspase-3 and transforming growth factor-beta1 gene expression as well as left ventricular histopathological changes including necrosis and fibrosis induced by doxorubicin. Collectively, our results suggest that resveratrol provides a significant protection against doxorubicin-induced cardiotoxicity and fibrosis in rats. Therefore, it may be used as a promising cardioprotective agent in patients treated with doxorubicin due to malignant diseases. So, further clinical trials are required to confirm these findings.     

Lysosomal hydrolases in reproductive organs during estrous cycle of the hamster

Changes in the total protein content and the activities of lysosomal hydrolases (arylsulfatase, acid phosphatases, β-glucuronidase, β-N-acetylhexosaminidase, α-L-fucosidase, and β-galactosidase) of the hamster genital tract during the 4 days of estrous cycle and in hormonally superovulated hamsters were measured. Levels of lysosomal hydrolases in uteri and uterine fluid changed significantly during the cycle. Similar changes were observed in uterine wet weight and uterine proteins. The pattern of enzyme activities in both the ovary and the oviduct were different from those in uteri. In the ovary, most enzyme activities and the total protein concentration remained elevated after ovulation. Protein concentration and enzyme activities were significantly higher in the ovary, oviduct, and uteri of superovulated hamsters as compared to controls.     

Phytochemical and Biological Activities in Limonium Species Collected in Different Biotopes of Tunisia

A particular interest is nowadays given to natural antioxidants occurring in foods which can reduce the risk of several diseases through their protective effect. The genus Limonium is widely distributed in different salt regions of Tunisia and known in traditional medicine for the presence of highly effective viral and bacterial replication inhibitors. Limonium leaves have possible beneficial effects on human health for their antioxidant activities and free radical scavenging abilities. To exploit the potential of plants from extreme environments as new sources of natural antioxidants, we studied the extracts from leaves of eight Limonium species growing in extreme environments in Tunisia. Antioxidant molecules (polyphenols, flavonoids, flavonols, ascorbate, tocopherols), in vitro (DPPH, ORAC) and ex vivo antioxidant potential on human erythrocytes, antioxidant enzymes activities (superoxide dismutase, peroxidases, glutathione reductase) were evaluated to identify the species with the best antioxidant capacity. The results showed variability among the species considered in function of the environmental conditions of their natural biotopes, as for the antioxidants measured. In particular, L. vulgare from Oued Rane biotope, characterized by dryness and high temperatures, was the species with the highest enzymatic activity and antioxidant capacity, making it interesting as possible edible halophyte plant or as food complement.