Synthesis,Conformational and Configurational Studies of Some New Acetylated Glycosides of 2-Thio-3-aryl-4(3H)-quinazolinones,Their Thiono and 3,1-Benzothiazin-2,4-dithione

Abstract

A series of some new acetylated S-glycosides of 2-thioxoquinazolin-4-ones, their thiono analogues and 3,1-benzothazin-2,4-dithione derivatives, including a D-glucose and a D-galactose derivatives and a D-xylose, and an L-arabinose derivatives have been synthesized. The conformation and configuration of these carbohydrate derivatives were determined by analysing their ¹H and ¹³C NMR chemical shifts and coupling constants. The biological activity of these compounds has been studied.     

Morphology of three new marine Frontonia species (Ciliophora; Peniculida) with note on the phylogeny of this genus

Members of the ciliate genus Frontonia are common colonizers of periphytic communities in aquatic biotopes. Recent studies indicate that their species diversity is higher than previously supposed. In this study the morphology and infraciliature of three new species, Frontonia sinica spec. nov., F. pusilla spec. nov., and F. elegans spec. nov., isolated from coastal waters of China, were investigated using live observation and silver impregnation methods. Frontonia sinica differs from its congeners by the following combination of characters: ellipsoidal body, about 116 somatic and five or six vestibular kineties, peniculi 1 and 2 four-rowed, peniculus 3 two-rowed, and a single contractile vacuole. Frontonia pusilla has about 72 somatic kineties, four-rowed peniculi 1 and 2, a two-rowed peniculus 3, and two contractile vacuoles. Frontonia elegans has 73 somatic kineties, four-rowed peniculi 1 and 2, a three-rowed peniculus 3, and two contractile vacuoles. In the present work, six new small-subunit rRNA gene sequences of six Frontonia species are used to construct the phylogenetic trees. Our phylogenetic analysis supports that the genus Frontonia may be paraphyletic. Meanwhile, no pattern of correlation could be found between the structures of peniculi and the phylogenetic relationships of Frontonia species in the present study.     

Utility of Dexrazoxane for the Attenuation of Epirubicin-Induced Genetic Alterations in Mouse Germ Cells

Dexrazoxane has been approved to treat anthracycline-induced cardiomyopathy and extravasation. However, the effect of dexrazoxane on epirubicin-induced genetic alterations in germ cells has not yet been reported. Thus, the aim of this study was to determine whether dexrazoxane modulates epirubicin-induced genetic damage in the germ cells of male mice. Our results show that dexrazoxane was not genotoxic at the tested doses. Furthermore, it protected mouse germ cells against epirubicin-induced genetic alterations as detected by the reduction in disomic and diploid sperm, spermatogonial chromosomal aberrations, and abnormal sperm heads. The attenuating effect of dexrazoxane was greater at higher dose, indicating a dose-dependent effect. Moreover, sperm motility and count were ameliorated by dexrazoxane pretreatment. Epirubicin induced marked biochemical changes characteristic of oxidative DNA damage including elevated 8-hydroxy-2ʹ-deoxyguanosine levels and reduction in reduced glutathione. Pretreatment of mice with dexrazoxane before epirubicin challenge restored these altered endpoints. We conclude that dexrazoxane may efficiently mitigate the epirubicin insult in male germ cells, and prevent the enhanced risk of abnormal reproductive outcomes and associated health risks. Thus, pretreating patients with dexrazoxane prior to epirubicin may efficiently preserve not only sperm quality but also prevent the transmission of genetic damage to future generations.     

Risk factors associated with E. coli causing neonatal calf diarrhea

Calf diarrhea is one of the major health challenges in cattle herds. The bacteriological examination of fecal samples collected from apparently healthy and diarrheic calves' revealed isolation of 26 E. coli isolates out of 56 calves with an incidence of 46.4%. Serogroups O1, O26, O44, O55, O115, O119, O125, O146, and O151 were identified from the collected fecal samples. Using PCR all isolates was positive for ompA gene species specific for E. coli. While stx1 and eaeA genes detected with incidence of 3.8 and 19.2% respectively from the isolates. The presence of stx2 gene was negative in the fecal isolates. Among colostrum samples 4 E. coli isolates were detected and serogrouped to O26, O55 and O119. They were negative for eaeA, stx1 and stx2 except strain number 4 (O55) was positive for stx1. E. coli strains were sensitive to norfloxacin (80.7%) and resistant to ampicillin and cefotaxime (100% each). Based on our findings, there was no association between occurrence of E. coli and age of calf (2–14 days), while bottle feeding calf colostrum may be a source of E. coli contamination.     

Responses of Glossina austeni to sticky panels and odours

The responses of male tsetse Glossina austeni Newstead (Diptera: Glossinidae) towards blue and white sticky legged panels, baited with odour attractants, and towards modified panels were studied in the Jozani forest of Unguja Island, Zanzibar. Increasing the height of the body of a standard panel from 30 to 60 or 90 cm, increased the catch two-fold. Increasing the height of the legs (from 15 to 60 or 120 cm) or raising the device more than 5 cm above the ground reduced the catch significantly. The legs of the panels were the preferred landing sites of the flies, irrespective of the height of the body of the panel. Acetone (300 mg/h) combined with cow urine (60-130 mg/h) significantly increased the catches two- to threefold during the rainy season, but not during the dry season. Acetone had no effect during the dry season and its effect during the rainy season was less consistent. There was no effect of octenol (2.5-12.5 mg/h), used alone or in combination with acetone. Likewise, the catch did not increase through the addition of cow sebum, pig urine (60-860 mg/h), pig urine combined with acetone and octenol. The observed seasonal differences in the response of G. austeni towards odours are discussed in relation to host location strategies.     

Discovery of new VEGFR-2 inhibitors based on bis([1, 2, 4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives as anticancer agents and apoptosis inducers

Herein, a new wave of bis([1, 2, 4]triazolo)[4,3-a:3'',4''-c]quinoxaline derivatives have been successfully designed and synthesised. The synthesised derivatives were biologically investigated for their cytotoxic activities against HepG2 and MCF-7. Also, the tested compounds were further examined in vitro for their VEGFR-2 inhibitory activity. The most promising derivative 23j was further investigated for its apoptotic behaviour in HepG2 cell lines using flow cytometric and western-plot analyses. Additional in-silico studies were performed to predict how the synthesised compounds can bind to VEGFR-2 and to determine the drug-likeness profiling of these derivatives. The results revealed that compounds 23a, 23i, 23j, 23l, and 23n displayed the highest antiproliferative activities against the two cell lines with IC₅₀ values ranging from 6.4 to 19.4 µM. Furthermore, compounds 23a, 23d, 23h, 23i, 23j, 23l, 23 m, and 23n showed the highest VEGFR-2 inhibitory activities with IC₅₀ values ranging from 3.7 to 11.8 nM, comparing to sorafenib (IC₅₀ = 3.12 nM). Moreover, compound 23j arrested the HepG2 cell growth at the G2/M phase and induced apoptosis by 40.12% compared to the control cells (7.07%). As well, such compound showed a significant increase in the level of caspase-3 (1.36-fold), caspase-9 (2.80-fold), and BAX (1.65-fold), and exhibited a significant decrease in Bcl-2 level (2.63-fold).     

The Toxoplasma gondii type-II NADH dehydrogenase TgNDH2-I is inhibited by 1-hydroxy-2-alkyl-4(1H)quinolones

The apicomplexan parasite Toxoplasma gondii does not possess complex I of the mitochondrial respiratory chain, but has two genes encoding rotenone-insensitive, non-proton pumping type-II NADH dehydrogenases (NDH2s). The absence of such "alternative" NADH dehydrogenases in the human host defines these enzymes as potential drug targets. TgNDH2-I and TgNDH2-II are constitutively expressed in tachyzoites and bradyzoites and are localized to the mitochondrion as shown by epitope tagging. Functional expression of TgNDH2-I in the yeast Yarrowia lipolytica as an internal enzyme, with the active site facing the mitochondrial matrix, permitted growth in the presence of the complex I inhibitor DQA. Bisubstrate kinetics of TgNDH2-I measured within Y. lipolytica mitochondrial membrane preparations were in accordance with a ping-pong mechanism. Using inhibition kinetics we demonstrate here that 1-hydroxy-2-alkyl-4(1)quinolones with long alkyl chains of C(12) (HDQ) and C(14) are high affinity inhibitors for TgNDH2-I, while compounds with shorter side chains (C(5) and C(6)) displayed significantly higher IC(50) values. The efficiency of the various quinolone derivatives to inhibit TgNDH2-I enzyme activity mirrors their inhibitory potency in vivo, suggesting that a long acyl site chain is critical for the inhibitory potential of these compounds.     

Melanism and coat colour polymorphism in the Egyptian Wolf Canis lupaster Hemprich & Ehrenberg (Carnivora: Canidae) from Egypt

The Egyptian Wolf Canis lupaster was recently rediscovered as a distinct species on the basis of both morphologic and molecular genetic evidence. Phenotypical variability, including coat colour of this species across its vast, ecologically diverse range is yet to be investigated. In this paper, we present the first record of melanistic individuals of this species and compare their morphological characters and mitochondrial cytochrome b DNA sequences with those of typically coloured Canis lupaster and other closely related canids to verify their identity. We also study pelage polymorphism in a population of this species in the Egyptian Nile Valley and the Nile Delta and define its different colour variants. The typical colour, as well as the rare, very light and reddish coat colours are described. We discuss the possibility that the observed coat colour polymorphism is the result of hybridisation with the domestic dog and their potential adaptive significance.     

Long-wavelength absorbing and fluorescent chameleon labels for proteins, peptides, and amines

Long-wavelength absorbing labels that change their color and fluorescence upon conjugation to proteins and other biomolecules provide two critical advantages over the wealth of conventional amine-reactive labels. At first, the progress of the labeling reaction can be monitored continuously either visually or by spectrometry without prior purification. Then, the labeled biomolecule can be investigated with red or near-infrared light, which minimizes background interference in biological samples. These unique characteristics are met by a group of long-wavelength absorbing cyanine dyes carrying a reactive chloro substituent for nucleophilic substitution with primary amines, which is accompanied by a color change from green to blue. In addition to this so-called chameleon effect, the dyes display an increase in fluorescence during the labeling reaction. Despite their structural similarity, the reactivity of the dyes differs strongly. The fastest labeling kinetics is observed with dye S 0378 as its five-membered ring affords a stabilizing effect on the intermediate carbocation during an S(N)1-type of nucleophilic substitution. The reaction mechanism of the amine-reactive cyanine dyes provides a blueprint for the design of future long-wavelength absorbing chameleon dyes.