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51.
Tarfah Al-Warhi Adil Aldhahrani Fayez Althobaiti Eman Fayad Ola A. Abu Ali Sarah Albogami Ali H. Abu Almaaty Amgad I. M. Khedr Syed Nasir Abbas Bukhari Islam Zaki 《Molecules (Basel, Switzerland)》2022,27(12)
A novel series of amides based TMP moiety was designed, synthesized and evaluated for their antiproliferative as well as enzyme inhibition activity. Compounds 6a and 6b showed remarkable cytotoxic activity against HepG2 cells with IC50 values 0.65 and 0.92 μM, respectively compared with SAHA and CA-4 as reference compounds. In addition, compound 6a demonstrated good HDAC-tubulin dual inhibition activity as it showed better HDAC activity as well as anti-tubulin activity. Moreover, compound 6a exhibited G2/M phase arrest and pre-G1 apoptosis as demonstrated by cell cycle analysis and Annexin V assays. Further apoptosis studies demonstrated that compound 6a boosted the level of caspase 3/7. Caspase 3/7 activation and apoptosis induction were evidenced by decrease in mitochondrial permeability suggesting that activation of caspase 3/7 may occur via mitochondrial apoptotic pathway. 相似文献
52.
Rabab M. Amer Amira Kamel Eltokhy Rasha Osama Elesawy Amany Nagy Barakat Eman Basha Omnia Safwat Eldeeb Alshimaa Aboalsoud Nancy Mohamed Elgharabawy Radwa Ismail 《Molecules (Basel, Switzerland)》2022,27(12)
Introduction. Vigabatrin (VGB) is an antiepileptic drug that acts to irreversibly inhibit the γ-aminobutyric acid (GABA) transaminase enzyme, elevating GABA levels. Broad studies have established that long-term treatment and/or high doses of VGB lead to variable visual defects. However, little attention has been paid to its other side effects, especially those demonstrating cerebellar involvement. Sodium glucose-linked co-transporter 2 (SGLT2) inhibitors are antidiabetic agents with protective effects far greater than expected based on their anti-hyperglycemic effect. Method. Our study herein was designed to investigate the possible ameliorative effect of empagliflozin, the SGLT2 inhibitors, in VGB-induced cerebellar toxicity. A total of 40 male Wistar rats were allocated equally into 4 groups: Group I: control group; Group II: VGB group; Group III empagliflozin treated VGB group; and Group IV: empagliflozin treated group. All groups were subjected to the detection of cerebellar messenger RNA gene expression of silent mating type information regulation 2 homolog 1 (SIRT1) and Nucleoporin p62 (P62). Mammalian target of rapamycin (mTOR), adenosine monophosphate-activated protein kinase (AMPK), and beclin1 levels were assessed by the ELISA technique while malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected spectrophotometrically. Immuno-histochemical studies, focusing on glial fibrillary acidic protein (GFAP) and S100 were performed, and the optical color density and the mean area percentage of GFAP positive astrocytes and the number of S 100 positive cells were also counted. Results. Following empagliflozin treatment, we documented significant upregulation of both SIRT1 and P62 mRNA gene expression. Additionally, AMPK, Beclin1 levels, and SOD activity were significantly improved, while both mTOR and MDA levels were significantly reduced. Conclusions. We concluded for the first time that empagliflozin efficiently ameliorated the VGB-induced disrupted mTOR/AMPK/SIRT-1 signaling axis with subsequent improvement of the autophagy machinery and mitigation of the oxidative and inflammatory cellular environment, paving the way for an innovative therapeutic potential in managing VGB-induced neurotoxicity. 相似文献
53.
Mohammed Alqarni Nader Ibrahim Namazi Sameer Alshehri Ibrahim A. Naguib Amal M. Alsubaiyel Kumar Venkatesan Eman Mohamed Elmokadem Mahboubeh Pishnamazi Mohammed A. S. Abourehab 《Molecules (Basel, Switzerland)》2022,27(14)
Industrial-based application of supercritical CO2 (SCCO2) has emerged as a promising technology in numerous scientific fields due to offering brilliant advantages, such as simplicity of application, eco-friendliness, and high performance. Loxoprofen sodium (chemical formula C15H18O3) is known as an efficient nonsteroidal anti-inflammatory drug (NSAID), which has been long propounded as an effective alleviator for various painful disorders like musculoskeletal conditions. Although experimental research plays an important role in obtaining drug solubility in SCCO2, the emergence of operational disadvantages such as high cost and long-time process duration has motivated the researchers to develop mathematical models based on artificial intelligence (AI) to predict this important parameter. Three distinct models have been used on the data in this work, all of which were based on decision trees: K-nearest neighbors (KNN), NU support vector machine (NU-SVR), and Gaussian process regression (GPR). The data set has two input characteristics, P (pressure) and T (temperature), and a single output, Y = solubility. After implementing and fine-tuning to the hyperparameters of these ensemble models, their performance has been evaluated using a variety of measures. The R-squared scores of all three models are greater than 0.9, however, the RMSE error rates are 1.879 × 10−4, 7.814 × 10−5, and 1.664 × 10−4 for the KNN, NU-SVR, and GPR models, respectively. MAE metrics of 1.116 × 10−4, 6.197 × 10−5, and 8.777 × 10−5errors were also discovered for the KNN, NU-SVR, and GPR models, respectively. A study was also carried out to determine the best quantity of solubility, which can be referred to as the (x1 = 40.0, x2 = 338.0, Y = 1.27 × 10−3) vector. 相似文献
54.
New Ni(II), Pd(II) and Pt(II) complexes coordinated to azo pyrazolone ligand with a potent anti‐tumor activity: Synthesis,characterization, DFT and DNA cleavage studies 下载免费PDF全文
Eman A. Bakr Gad B. Al‐Hefnawy Mohamed K. Awad Hossam H. Abd‐Elatty Mohamed S. Youssef 《应用有机金属化学》2018,32(2)
The absolute necessity to fight some class of tumor is perceived as serious health concerns, so the discovery and development of effective anticancer agents are urgently needed. (E)‐4‐((2‐hydroxyphenyl)diazenyl)‐3‐phenyl‐1H‐pyrazol‐5(4H)‐one, HL, and its Ni(II), Pd(II) and Pt(II) complexes were synthesized and the biological activity was evaluated for antitumor, antioxidant and antimicrobial activity as well as DNA cleavage. Their structures were assigned depending on the elemental analysis, conductivity, magnetic moment, spectral measurements (IR, 1HNMR, mass and UV–Vis) and thermal analysis. 3D molecular modeling using DFT method confirmed that the geometrical structures agree well with the suggested experimental ones. The antitumor activity was evaluated against four different cell lines using MTT assay. The ligand HL showed a potent cytotoxic activity compared to 5‐fluorouracil as a reference drug. For metal complexes, the order of activity was: Pd(II) > Ni(II) > Pt(II). A remarkable antioxidant activity for the ligand HL was recorded. It was higher than that of the metal complexes. Results of antimicrobial experiments revealed that all compounds were moderate to highly active against selected bacterial strains but inactive as antifungal except Pd(II) which showed a moderate antifungal activity. Gel electrophoresis showed insignificant nucleases activity for the ligand or its metal complexes even in the presence of H2O2 providing protection of DNA from damage. The antitumor activity of our compounds may be not due to DNA cleavage but may be referred to a mechanism similar to that of 5‐fluorouracil which interfere with DNA replication. The present work suggests the use of this ligand in the design and development of new anticancer drugs. 相似文献
55.
Divya Ganesan Eman Al-Sayed Abhishek Albert Eldho Paul Abdel Nasser B. Singab 《Natural product research》2018,32(11):1274-1280
Phytochemicals serve as potential therapeutic agents for the prevention and treatment of diseases. In this study, we elucidate the renoprotective activity of compounds isolated from Eucalyptus globulus and Melaleuca styphelioides extracts in glucose- and oxalate-challenged NRK-49F cell model. The antioxidant potential of isolated compounds was evaluated based on their effect on antioxidant enzyme activities and lipid peroxidation levels. The results demonstrated that exposure of NRK-49F cells to glucose and oxalate stress augmented cell damage and attenuated antioxidant enzyme activities. The phytochemicals 2,2,8-trimethyl-6-formyl-chrom-3-ene-7-O-β-D-glucopyranoside, Cornusiin B and tellimagrandin I treatment restored antioxidant enzyme activity, significantly lowered lipid peroxidation levels and effectively protected cells from glucose and oxalate stress equivalent to the known antioxidant, N-acetyl cysteine. Pterocarinin A significantly reversed cellular damage owing to glucose stress. In conclusion, the compounds isolated from E. globulus and M. styphelioides showed potential cytoprotective and anti-oxidative property against glucose- and oxalate-induced oxidative stress in NRK-49F cells. 相似文献
56.
L. V. Batog V. Yu. Rozhkov L. S. Konstantinova V. E. Eman M. O. Dekaprilevich Yu. T. Struchkov S. E. Semenov O. V. Lebedev L. I. Khmel'nitskii 《Russian Chemical Bulletin》1996,45(5):1189-1193
The oxidative cyclocondensation of 3,4-diaminofurazan and 4,4-diamino-3,3-azofurazan with dibromoisocyanurate afforded macrocyclec polydiazenofurazans. The reaction can be directed towards the formation of both the four-membered cycle alone or the three-, six-, and eight-membered macrocycles.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1250–1254, May, 1996.Deceased in 1995. 相似文献
57.
Bertelli M El-Bastawissy E Knaggs MH Barrett MP Hanau S Gilbert IH 《Journal of computer-aided molecular design》2001,15(5):465-475
A number of triphenylmethane derivatives have been screened against 6-phosphogluconate dehydrogenase from Trypanosoma brucei and sheep liver. Some of these compounds show good inhibition of the enzymes and also selectivity towards the parasite enzyme. Modelling was undertaken to dock the compounds into the active sites of both enzymes. Using a combination of DOCK 3.5 and FLEXIDOCK a correlation was obtained between docking score and both activity for the enzymes and selectivity. Visualisation of the docked structures of the inhibitors in the active sites of the enzymes yielded a possible explanation of the selectivity for the parasite enzyme. 相似文献
58.
Adel A.-H. Abdel-Rahman Ahmed E.-S. Abdel-Megied Mohamed A. M. Hawata Eman R. Kasem Mohamed T. Shabaan 《Monatshefte für Chemie / Chemical Monthly》2007,16(6):889-897
Chalcones were synthesized by a base catalyzed Claisen-Schmidt condensation reaction. Bromination of chalcones afforded the dibromo derivatives. Monobromo derivatives could be obtained
by treating the corresponding dibromochalcones with dry benzene in the presence of triethylamine. Pyrazole derivatives were
obtained by refluxing of dibromochalcones with phenylhydrazine or 2,4-dinitrophenylhydrazine in dry pyridine. Chalcones were
treated with hydrazine hydrate or phenyl hydrazine in ethanol to afford Δ
2-pyrazolines and N-phenyl-Δ
2-pyrazolines. Condensation of chalcones with hydroxylamine hydrochloride or thiourea in ethanolic sodium hydroxide solution
gave 4,5-dihydroisoxazoles and 5,6-dihydropyrimidine-2-(1H)-thiones. The prepared compounds were tested for antimicrobial activity against four different bacterial species displaying
different degrees of antibacterial activities or inhibitory actions. 相似文献
59.
Jan C. van Dam Michael R. Eman Johannes Frank Hans C. Lange Gijs W. K. van Dedem Sef J. Heijnen 《Analytica chimica acta》2002,460(2):307-218
The purpose of this study is to selectively and quantitatively analyze several glycolytic intermediates in cells of Saccharomyces cerevisiae using high-performance anion exchange chromatography (HPAEC) coupled to electrospray ionization tandem mass spectrometry for the analysis. A sodium hydroxide gradient is used to separate the glycolytic compounds and after the column sodium hydroxide is reduced by proton exchange with a membrane device prior to introduction to the mass spectrometer. The detection limits for 10 μl samples are down to the 0.4–5 pmol range. This corresponds for the intracellular metabolites to a range of 2–20 nmol per gram biomass dry weight (DW). Standard addition did reveal some influence of the sample matrix on the measured concentrations. Separation and analysis is hardly affected by the high sulfate and phosphate concentrations (1 mM) in the fermentation medium and by the intracellular matrix. Validation of the glucose-6-phosphosphate LC–MS–MS analysis results with enzymatic analysis showed an excellent agreement between the two methods. The suitability of the method was clearly shown by analyzing a series of steady state S. cerevisiae samples from a carbon limited aerobic chemostat culture. 相似文献
60.
Ahmed A. Abdel-Khalek El-Said M. Sayyah Eman S. H. Khalid 《Transition Metal Chemistry》1993,18(6):555-558
Summary The kinetics of oxidation of [CoII(EDTA)]2- (EDTA = ethylenediaminetetraacetate) by N-bromosuccinimide (NBS) in aqueous solution obey the equation: Rate = k
2
K
3[CoII]T[NBS]/{1 + [H+]/K
2 + K
3[NBS]} where k
2 is the rate constant for the electron-transfer process, K
2 the equilibrium constant for the dissociation of [CoII(EDTAH)(H2O)]– to [CoII(EDTA)(OH)]3– and K
3 the pre-equilibrium formation constant. The activation parameters are reported. It is proposed that electron transfer proceeds via an inner-sphere mechanism with the formation of an intermediate which slowly generates hexadentate[CoIII(EDTA)]–.Abstracted from the M.Sc. thesis of Eman S. H. Khaled. 相似文献