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排序方式: 共有373条查询结果,搜索用时 15 毫秒
71.
Zahran MA Salem TA Samaka RM Agwa HS Awad AR 《Bioorganic & medicinal chemistry》2008,16(22):9708-9718
A series of 16 novel thalidomide sulfur analogs containing one and two sulfur atoms 2 and 4-18, respectively, were designed and synthesized. These compounds were screened for in vitro antitumor activity against Ehrlich ascites carcinoma (EAC) cell line and exhibited potent cytotoxic activity. On the bases of the obtained results for in vitro cytotoxic activity, thalidomide sulfur analogs containing two sulfur atoms 8, 9, 13 and 14 were selected and tested in vivo against EAC-induced solid tumor in female mice compared to thalidomide 1 as well as its analog 2 and exhibited a highly significant reduction in tumor volume (TV). Results illustrated the antioxidative activity of these compounds as the level of hepatic lipid peroxidation decreased and levels of antioxidant enzymes like superoxide dismutase (SOD) and catalase were elevated. The histopathological investigations revealed that thalidomide sulfur analogs 2, 8, 9, 13 and 14 have antimitotic, apoptotic and necrotic activities against solid tumor. These compounds lead to increase of Fas-L expression. The immunohistochemical studies showed a decrease in Ki67 and vascular endothelial growth factor (VEGF) staining in tumor cells from treated-animals when compared with non-treated groups, which suggests an inhibition of tumor proliferation rate and angiogenic process associated with tumor growth. Compounds 9 and 13 were the most potent compounds in tumor necrosis without liver necrosis. At the same time, treatment with compound 9 resulted in liver degeneration. 相似文献
72.
Abdallah E. Abdallah Reda R. Mabrouk Maged Mohammed Saleh Al Ward Sally I. Eissa Eslam B. Elkaeed Ahmed B. M. Mehany Mariam A. Abo-Saif Ola A. El-Feky Mohamed S. Alesawy Mohamed Ayman El-Zahabi 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):573
Based on quinazoline, quinoxaline, and nitrobenzene scaffolds and on pharmacophoric features of VEGFR-2 inhibitors, 17 novel compounds were designed and synthesised. VEGFR-2 IC50 values ranged from 60.00 to 123.85 nM for the new derivatives compared to 54.00 nM for sorafenib. Compounds 15a, 15b, and 15d showed IC50 from 17.39 to 47.10 µM against human cancer cell lines; hepatocellular carcinoma (HepG2), prostate cancer (PC3), and breast cancer (MCF-7). Meanwhile, the first in terms of VEGFR-2 inhibition was compound 15d which came second with regard to antitumor assay with IC50 = 24.10, 40.90, and 33.40 µM against aforementioned cell lines, respectively. Furthermore, Compound 15d increased apoptosis rate of HepG2 from 1.20 to 12.46% as it significantly increased levels of Caspase-3, BAX, and P53 from 49.6274, 40.62, and 42.84 to 561.427, 395.04, and 415.027 pg/mL, respectively. Moreover, 15d showed IC50 of 253 and 381 nM against HER2 and FGFR, respectively. 相似文献
73.
Tamar Harel Gozde Yesil Yavuz Bayram Zeynep Coban-Akdemir Wu-Lin Charng Ender Karaca Ali Al?Asmari Mohammad?K. Eldomery Jill?V. Hunter Shalini?N. Jhangiani Jill?A. Rosenfeld Davut Pehlivan Ayman?W. El-Hattab Mohammed?A. Saleh Charles?A. LeDuc Donna Muzny Eric Boerwinkle Baylor-Hopkins Center for Mendelian Genomics Richard?A. Gibbs Wendy?K. Chung Yaping Yang John?W. Belmont James?R. Lupski 《American journal of human genetics》2016,98(3):562-570
The paradigm of a single gene associated with one specific phenotype and mode of inheritance has been repeatedly challenged. Genotype-phenotype correlations can often be traced to different mutation types, localization of the variants in distinct protein domains, or the trigger of or escape from nonsense-mediated decay. Using whole-exome sequencing, we identified homozygous variants in EMC1 that segregated with a phenotype of developmental delay, hypotonia, scoliosis, and cerebellar atrophy in three families. In addition, a de novo heterozygous EMC1 variant was seen in an individual with a similar clinical and MRI imaging phenotype. EMC1 encodes a member of the endoplasmic reticulum (ER)-membrane protein complex (EMC), an evolutionarily conserved complex that has been proposed to have multiple roles in ER-associated degradation, ER-mitochondria tethering, and proper assembly of multi-pass transmembrane proteins. Perturbations of protein folding and organelle crosstalk have been implicated in neurodegenerative processes including cerebellar atrophy. We propose EMC1 as a gene in which either biallelic or monoallelic variants might lead to a syndrome including intellectual disability and preferential degeneration of the cerebellum. 相似文献
74.
The everted rat intestinal‐sac model was utilized to assess the effect of post‐prandial conditions on the stereoselective intestinal metabolism of halofantrine to its active metabolite desbutylhalofantrine. Everted intestinal sacs were incubated with (±)‐halofantrine HCl in the presence of simulated bile solution (containing lecithin, lipase and cholesterol) and lipids to mimic post‐prandial conditions in the small intestine. The halofantrine enantiomer concentrations in intestinal sacs were relatively constant in the presence of bile, but decreased significantly on addition of lipids to the incubation media. Formation of desbutylhalofantrine enantiomers was inversely proportional to bile concentration whereas addition of lipids in the presence of bile caused a significant decrease in desbutylhalofantrine:halofantrine ratio of (?) enantiomers. Pre‐treatment of rats with peanut oil had no significant effect on desbutylhalofantrine formation in the incubated sacs or microsomal preparations, nor did it affect the expression of intestinal cytochrome P450. Addition of extra cholesterol to the bile incubations caused a significant increase in tissue halofantrine and desbutylhalofantrine concentrations, which as for lower cholesterol, were diminished on addition of other lipids. The results were consistent with previous in vivo evaluations showing that the desbutylhalofantrine to halofantrine ratio was decreased by the ingestion of a high fat meal. Chirality, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
75.
Mazhar Ali Nasir Masood Hafiz Muhammad Rashad Javeed Ibrahim Al-Ashkar Khalid F. Almutairi Liyun Liu Muhammad Aqeel Sarwar Karthika Rajendran Ayman EL Sabagh 《Phyton》2022,91(10):2235-2248
Soil amendments containing carbonized materials increase the soil carbon reservoir, influence plant productivity,
and, ultimately, help to clean the environment. There is data on the effect of such additions on soil physicochemical
properties or plant growth, but few studies have focused on how these carbonized materials are distributed by termite species in the soil ecosystem. It is the first comprehensive study of the transportation of biochar (BC) by termite
species under tropical environmental conditions in Pakistan. The present study was carried out to test the hypothesis
that if termite species I) were involved in the distribution of biochar particles II) if yes, then how far these particles
were transported during the study period (10 days) and III) check their preference between the enriched BC (EBC)
and non-enriched BC. BC was enriched with the cattle slurry after its pyrolysis in the study. The results showed that
EBC particles were significantly more widely distributed than non-enriched BC particles, but both types of BC were
transported more than 4 cm (ring 4) within 10 days (at the end of the experiment). The current study also revealed
that EBC was easily attached to the setae, cuticle, and legs of termites, implying that it could potentially be transported over a greater distance. Furthermore, transportation of EBC over larger distances indicated a potential preference of termite species between the EBC and BC particles. During the study, however, the preference among the
termite species was also observed. Under the prevailing study conditions, the Coptotermes heimi and Heteroterme
indicola species transported the EBC further than Microtermes obesi and Odontotermes obesus. These findings
revealed that transportation preferences were observed among the four termite species. In conclusion, the current
study found that termites were involved in the distribution of BC particles, with a preference for EBC and that these
have the potential to transport BC particles more than 4 cm within 10 days. Furthermore, two species Coptotermes
heimi and Heteroterme indicola may be more suitable candidates for EBC transpiration in Pakistani soils. It was
necessary to conduct additional research into the effect of temperature on the transportation process. 相似文献
76.
Mohamed Elagawany Ayman Abo Elmaaty Ahmed Mostafa Noura M. Abo Shama Eman Y. Santali Bahaa Elgendy Ahmed A. Al-Karmalawy 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):2112
The global outbreak of the COVID-19 pandemic provokes scientists to make a prompt development of new effective therapeutic interventions for the battle against SARS-CoV-2. A new series of N-(5-nitrothiazol-2-yl)-carboxamido derivatives were designed and synthesised based on the structural optimisation principle of the SARS-CoV Mpro co-crystallized WR1 inhibitor. Notably, compound 3b achieved the most promising anti-SARS-CoV-2 activity with an IC50 value of 174.7 µg/mL. On the other hand, compounds 3a, 3b, and 3c showed very promising SARS-CoV-2 Mpro inhibitory effects with IC50 values of 4.67, 5.12, and 11.90 µg/mL, respectively. Compound 3b docking score was very promising (−6.94 kcal/mol) and its binding mode was nearly similar to that of WR1. Besides, the molecular dynamics (MD) simulations of compound 3b showed its great stability inside the binding pocket until around 40 ns. Finally, a very promising SAR was concluded to help to design more powerful SARS-CoV-2 Mpro inhibitors shortly. 相似文献
77.
Sherin Y. Naiem Ayman E. Badran Mohamed S. Boghdady Bandar S. Aljuaid Ahmed M. El-Shehawi Heba M. Salem Amira M. El-Tahan Hany E. Ismail 《Saudi Journal of Biological Sciences》2022,29(4):2645-2655
The current experiment was adopted during the summer 2018, fall 2018/2019 and summer 2019 respectively at the Experimental Farm of Baloza station, Desert Research Center. North Sinai Governorate, Egypt to study the effect of different doses of irradiation (0, 20, 30 and 40 Gy), three irrigation levels (100, 80 and 60% field capacity on growth, yield and its quality of some potato cultivars (Spunta, Cara, Caruso and Hermes). Treated Spunta cultivar pre planting with 20 (Gy) and irrigated with 80% field capacity was the best treatment for increasing number of aerial stem/plants, leaf area, total chlorophyll in leaves, average tuber weight, and total yield/fed. Hermes cultivar with 20 (Gy) and irrigation level of 80% was the best for increasing dry matter content in tuber in both mutagenic generations. 相似文献
78.
Alexandra Charruyer Tracy Weisenberger Hang Li Ayman Khalifa Andrew W. Schroeder Annika Belzer Ruby Ghadially 《Aging cell》2021,20(2)
With age, the epidermis becomes hypoplastic and hypoproliferative. Hypoproliferation due to aging has been associated with decreased stem cell (SC) self‐renewal in multiple murine tissues. The fate of SC self‐renewal divisions can be asymmetric (one SC, one committed progenitor) or symmetric (two SCs). Increased asymmetric SC self‐renewal has been observed in inflammatory‐mediated hyperproliferation, while increased symmetric SC self‐renewal has been observed in cancers. We analyzed SC self‐renewal divisions in aging human epidermis to better understand the role of SCs in the hypoproliferation of aging. In human subjects, neonatal to 78 years, there was an age‐dependent decrease in epidermal basal layer divisions. The balance of SC self‐renewal shifted toward symmetric SC self‐renewal, with a decline in asymmetric SC self‐renewal. Asymmetric SC divisions maintain epidermal stratification, and this decrease may contribute to the hypoplasia of aging skin. P53 decreases in multiple tissues with age, and p53 has been shown to promote asymmetric SC self‐renewal. Fewer aged than adult ALDH+CD44+ keratinocyte SCs exhibited p53 expression and activity and Nutlin‐3 (a p53 activator) returned p53 activity as well as asymmetric SC self‐renewal divisions to adult levels. Nutlin‐3 increased Notch signaling (NICD, Hes1) and DAPT inhibition of Notch activation prevented Nutlin‐3 (p53)‐induced asymmetric SC self‐renewal divisions in aged keratinocytes. These studies indicate a role for p53 in the decreased asymmetric SC divisions with age and suggest that in aged keratinocytes, Notch is required for p53‐induced asymmetric SC divisions. 相似文献
79.
80.
daCosta CJ Michel Sturgeon R Hamouda AK Blanton MP Baenziger JE 《Biochemical and biophysical research communications》2011,(3):456-460
The Cys-loop receptor super-family of neurotransmitter-gated ion channels mediates fast synaptic transmission throughout the human nervous system. These receptors exhibit widely varying pharmacologies, yet their structural characterization has relied heavily on their homology with the naturally abundant muscle-type Torpedo nicotinic acetylcholine receptor. Here we examine for the first time the structure of a human α4β2 neuronal nicotinic acetylcholine receptor. We show that human α4β2 nicotinic receptors adopt a secondary/tertiary fold similar to that of the Torpedo nicotinic receptor with a large proportion of both α-helix and β-sheet, but exhibit a substantially increased thermal stability. Both receptors bind agonist, but with different patterns of agonist recognition – particularly in the nature of the interactions between aromatic residues and the agonist quaternary amine functional group. By comparing α4β2 and Torpedo receptors, we begin to delineate their structural similarities and differences. 相似文献