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31.
Nawaf A. Alsaif Mohammed S. Taghour Mohammed M. Alanazi Ahmad J. Obaidullah Abdulrahman A. Al-Mehizia Manal M. Alanazi Saleh Aldawas Alaa Elwan Hazem Elkady 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):1093
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). 相似文献
32.
The Toxoplasma gondii type-II NADH dehydrogenase TgNDH2-I is inhibited by 1-hydroxy-2-alkyl-4(1H)quinolones 总被引:1,自引:0,他引:1
Lin SS Kerscher S Saleh A Brandt U Gross U Bohne W 《Biochimica et biophysica acta》2008,1777(11):1455-1462
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. 相似文献
33.
Since the end of 2018, the distribution of the reference tracer for the measurement of glomerular filtration rate (GFR), the 51Cr-EDTA, is no longer provided by radiopharmaceutical companies around the world. In this study, we propose to compare the measurement of glomerular filtration rate by 99mTc-DTPA to that by 51Cr-EDTA. A double estimation of GFR by plasma clearance was performed in 12 patients, 10 of which were referred for GFR calculation prior to possible kidney donation. Linear regression coefficients and intraclass correlation coefficient (ICC) were calculated for the GFR measurement by 99mTc-DTPA, and by MDRD, CKD-EPI and Cockcroft and Gault formulas, relative to the 51Cr-EDTA measurement. The clearance measurement with 99mTc-DTPA is on average 7.25 [2.00; 14.96] mL/min/1.73m2 higher than that of 51Cr-EDTA. The GFR measurement with 99mTc-DTPA showed a trend towards better agreement with the 51Cr-EDTA measurement in terms of linear regression parameters, but also in terms of ICC compared to the MDRD, CKD-EPI and Cockcroft and Gault methods. In conclusion, our study supports the use of the 99mTc-DTPA tracer in place of 51Cr-EDTA and shows a higher reliability compared to methods based on blood creatinine measurement. 相似文献
34.
Anthony D. Saleh Brittany A. Simone Juan Palazzo Jason E. Savage Yuri Sano Tu Dan Lianjin Jin Colin E. Champ Shuping Zhao Meng Lim Frederica Sotgia Kevin Camphausen Richard G. Pestell James B. Mitchell Michael P. Lisanti Nicole L. Simone 《Cell cycle (Georgetown, Tex.)》2013,12(12):1955-1963
Dietary modification such as caloric restriction (CR) has been shown to decrease tumor initiation and progression. We sought to determine if nutrient restriction could be used as a novel therapeutic intervention to enhance cytotoxic therapies such as radiation (IR) and alter the molecular profile of triple-negative breast cancer (TNBC), which displays a poor prognosis. In two murine models of TNBC, significant tumor regression is noted with IR or diet modification, and a greater regression is observed combining diet modification with IR. Two methods of diet modification were compared, and it was found that a daily 30% reduction in total calories provided more significant tumor regression than alternate day feeding. At the molecular level, tumors treated with CR and IR showed less proliferation and more apoptosis. cDNA array analysis demonstrated the IGF-1R pathway plays a key role in achieving this physiologic response, and multiple members of the IGF-1R pathway including IGF-1R, IRS, PIK3ca and mTOR were found to be downregulated. The innovative use of CR as a novel therapeutic option has the potential to change the biology of tumors and enhance the opportunity for clinical benefit in the treatment of patients with TNBC. 相似文献
35.
Mansour S. Alsaid Mostafa M. Ghorab Saleh I. Alqasoumi Maged S. Abdel-Kader 《Russian Journal of Bioorganic Chemistry》2016,42(5):567-573
A novel series of thiourea and carbamimidothioic acid derivatives was synthesized using natural alkaloid L-norephedrine as a starting material. Structures of the newly synthesized compounds were confirmed by analytical and spectral data. The synthesized compounds were evaluated in vitro for anticancer activity against the human breast (MCF-7), human liver (HEPG2), and human colon (HCT116) cancer cell lines. Best activity of the synthesized compounds was expressed against HEPG2, however, none of the compounds exceeded the IC50 of doxorubicin. The corresponding N-(1-(2-chloroacetoxy)-1-phenylpropan-2-yl)-N′-p-tolylcarbamimidothioic acid was the most potent compound and exhibited higher cytotoxic activity against the human colon cancer cell line (HCT116) when compared with the reference drug doxorubicin. Also, this compound was the most active against the MCF-7 cell line but less active than the positive control. 相似文献
36.
Small mitochondrial DNA molecules of wild abortive cytoplasm in rice are not necessarily associated with CMS 总被引:2,自引:0,他引:2
N. M. Saleh B. J. Mulligan E. C. Cocking H. S. Gupta 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1989,77(5):617-619
Summary Mitochondrial DNA was isolated from leaf tissue of both the cytoplasmic male sterile line of Indica rice variety V41, which carries wild abortive (WA) cytoplasm, and from the corresponding maintainer line. In addition to the main mitochondrial DNA, four small plasmid-like DNA molecules were detected in both the male sterile and fertile lines. Restriction analysis of total mitochondrial DNA from the male sterile and fertile lines showed DNA fragments unique to each. Our findings suggest that the four small mitochondrial DNA (mtDNA) molecules are conserved when WA cytoplasm is transferred into different nuclear backgrounds. However, there is no simple correlation between the presence/ absence of small mitochondrial DNA molecules and the expression of WA cytoplasmic male sterility (CMS). 相似文献
37.
Mostafa Saleh Mahmoud Younes Moustafa Sarhan Fouad Abdel-Hamid 《Zoology in the Middle East.》2018,64(3):195-206
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. 相似文献
38.
Chazenbalk G Bertolotto C Heneidi S Jumabay M Trivax B Aronowitz J Yoshimura K Simmons CF Dumesic DA Azziz R 《PloS one》2011,6(3):e17834
Introduction
Previous studies highlight a complex relationship between lineage and phenotype for adipose tissue macrophages (ATMs), adipose stem cells (ASCs), and adipocytes, suggesting a high degree of plasticity of these cells. In the present study, using a novel co-culture system, we further characterized the interaction between ATMs, ASCs and adipocytes.Research Design and Methods
Human adipocytes and the stromal vascular fraction containing ATMs and ASCs were isolated from human adipose tissue and co-cultured for 24 hours. FACS was used to characterize ATMs and ASCs before and after co-culture. Preadipocytes generated after co-culture were characterized by immunostaining for DLK (preadipocytes), CD14 and CD68 (ATMs), CD34 (ASCs), and Nile Red staining for lipid drops. qRT-PCR was used to quantify adipogenic markers such as C/EBPα and PPARγ. A novel fluorescent nanobead lineage tracing method was utilized before co-culture where fluorescent nanobeads were internalized by CD68 (+) ATMs.Results
Co-culture of adipocytes with ATMs and ASCs increased the formation of new preadipocytes, thereby increasing lipid accumulation and C/EBPα and PPARγ gene expression. Preadipocytes originating after co-culture were positive for markers of preadipocytes, ATMs and ASCs. Moreover, fluorescent nanobeads were internalized by ATMs before co-culture and the new preadipocytes formed after co-culture also contained fluorescent nanobeads, suggesting that new preadipocytes originated in part from ATMs. The formation of CD34(+)/CD68(+)/DLK (+) cell spheres supported the interaction of ATMs, ASCs and preadipocytes.Conclusions
Cross-talk between adipocytes, ATMs and ASCs promotes preadipocyte formation. The regulation of this novel adipogenic pathway involves differentiation of ATMs to preadipocytes. The presence of CD34(+)/CD68(+)/DLK(+) cells grouped in spheres suggest that paracrine interactions between these cell types plays an important role in the generation and proliferation of new preadipocytes. This phenomenon may reflect the in vivo plasticity of adipose tissue in which ATMs play an additional role during inflammation and other disease states. Understanding this novel pathway could influence adipogenesis, leading to new treatments for obesity, inflammation, and type 2 diabetes. 相似文献39.
Natalie Barnes Roger N. Bamber Graham Bennell Nils Cornelius David Glassom Sophie Conroy-Dalton Henderson Narriman Jiddawi Christine N. W. Lee Adriano Macia Daudi J. Msangameno Jos�� Paula Saleh Yahya Timothy J. Ferrero 《Biodiversity and Conservation》2011,20(10):2075-2109
The transboundary networks of Marine Protected Areas (MPAs) project, TRANSMAP, assessed local turnover and regional biodiversity across the East African Marine Ecoregion, where inter-governmental co-operation has been working to connect local MPAs. The benthic fauna in the three most dominant habitats on this coastline??beaches, mangroves and seagrasses??were studied in two Regions (Northern Region, 10?C13°S; Southern Region, 25?C28°S). Meiofaunal taxa were used as the model faunal group owing to their diversity and abundance across habitat types and environmental conditions. Meiofaunal abundance averaged 2,500 individuals 10 cm?2 and was generally higher in mangrove and seagrass sediments than on the beaches, and was significantly different between habitats × Regions. In total, 18 taxa were recorded with highest diversity in the beach samples. Diversity indices and assemblage structure were significantly different between habitats, but also Regions. Specific granulometric 1?? size classes, shore-height and number of rain days were the factors most significantly correlating with the observed assemblage patterns. Additionally, the size of a MPA and latitude (which correlated with MPA age, but not number of rain days), were the factors fitting best with meiofaunal assemblage patterns across the beaches, the habitat for which the most comprehensive data were generated. Sample diversity was higher in the Southern Region, and although within- and across-habitats diversity were similar across the Regions, the two Regions appeared to provide complementary habitats and supported different assemblages. Within the Regions, beaches (the only habitat for which more than one location was sampled) were significantly different between Locations, supporting the establishment of multiple protected locations of the same habitat within each transboundary MPA. 相似文献
40.
Gorris HH Saleh SM Groegel DB Ernst S Reiner K Mustroph H Wolfbeis OS 《Bioconjugate chemistry》2011,22(7):1433-1437
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. 相似文献