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51.
Wagdy M. Eldehna Mahmoud F. Abo-Ashour Hany S. Ibrahim Ghada H. Al-Ansary Hazem A. Ghabbour Mahmoud M. Elaasser 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):686-700
On account of their significance as apoptosis inducing agents, merging indole and 3-hydrazinoindolin-2-one scaffolds is a logic tactic for designing pro-apoptotic agents. Consequently, 27 hybrids (6a–r, 9a–f and 11a–c) were synthesised and evaluated for their cytotoxicity against MCF-7, HepG-2 and HCT-116 cancer cell lines. SAR studies unravelled that N-propylindole derivatives were the most active compounds such as 6n (MCF-7; IC50=1.04?µM), which displayed a significant decrease of cell population in the G2/M phase and significant increase in the early and late apoptosis by 19-folds in Annexin-V-FTIC assay. Also, 6n increased the expression of caspase-3, caspase-9, cytochrome C and Bax and decreased the expression of Bcl-2. Moreover, compounds 6i, 6j, 6n and 6q generated ROS by significant increase in the level of SOD and depletion of the levels of CAT and GSH-Px in MCF-7. 相似文献
52.
Victoria S. Haritos Michael S. Ching Hany Ghabrial Jorma T. Ahokas 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1997,693(2):379
A specific and useful method was developed for the determination of dexfenfluramine metabolism by microsomal systems utilising GC–MS. The synthesis of two metabolites 1-(3-trifluoromethylphenyl)propan-2-ol (‘alcohol') and 1-(3-trifluoromethylphenyl)-1,2-propanediol (‘diol') via straightforward routes, were confirmed by MS and NMR spectra. The conditions for extraction from alkalinised microsomal mixtures of the metabolites nordexfenfluramine, 1-(3-trifluoromethylphenyl)propan-2-one (‘ketone'), alcohol and diol, their conversion to trifluoroacetate derivatives and analysis by GC–MS–SIM are described. Calibration curves were constructed between 48 and 9662 nM and fitted to quadratic equations (r2>0.999). The method precision was good over low (121 nM) medium (2415 nM) and above medium (9662 nM) concentrations for all metabolites; the within- and day-to-day coefficients of variation ranged between 2.5–12.4% and 6.7–17.5%, respectively. The accuracy, measured as bias, was very good both within- and day-to-day (range: −0.4–12.6%, 0.8–18.9%). For most metabolites, the C.V. for the assay and bias increased at 121 nM. Dexfenfluramine metabolism by rat liver microsomes was investigated using the assay method and showed a concentration dependent increase in nordexfenfluramine and ketone metabolites over the substrate range of 5–200 μM. 相似文献
53.
Khaled R. A. Abdellatif Phoebe F. Lamie Hany A. Omar 《Journal of enzyme inhibition and medicinal chemistry》2016,31(2):318-324
In a new group of 3-methyl-2-phenyl-1-substituted-indole derivatives (10a–f), the indomethacin analogs were prepared via the Fisher indole synthesis reaction of propiophenone with appropriately substituted phenylhydrazine hydrochloride. This is followed by the insertion of the appropriate benzyl or benzoyl fragment. All the synthesized compounds were evaluated for their anti-inflammatory (in vitro and in vivo) and analgesic activities. The methanesulphonyl derivatives 10d, e and f showed the highest anti-inflammatory (in vitro and in vivo) and analgesic activities. In addition, molecular docking studies were performed on compounds 10a–f and the results were in agreement with that obtained from the in vitro COX inhibition assays. The significant anti-inflammatory and analgesic activities exhibited by 10d and 10e warrant continued preclinical development as potential anti-inflammatory and analgesic agents. 相似文献
54.
Hany Ahmed Fouad Hosam Mohamed Khalil Hammam El-Gepaly Osama Ahmed Fouad 《Archives Of Phytopathology And Plant Protection》2016,49(13-14):362-370
Recently, Tuta absoluta became one of the major pests that attack commercial tomato globally. Field test was done to evaluate the effect of different concentrations of nanosilica (NS) and jasmonic acid (JA), and compared them with indoxacrb (recommended insecticide) on reduction of damage rate caused by T. absoluta larvae under field conditions. Nanosilica (600 ppm) and indoxacrb (0.25 cm3/L) had the highest efficiency to reduce the rate of mines in the leaves. Jasmonic acid at rate 1.141 μM/plant showed a good reduction of number of fruits damaged. Nanosilica with 600 ppm concentration and Jasmonic acid at rate 1.141 μM/plant is used to control T. absoluta in the field. 相似文献
55.
Pantaleo A Ferru E Vono R Giribaldi G Lobina O Nepveu F Ibrahim H Nallet JP Carta F Mannu F Pippia P Campanella E Low PS Turrini F 《Free radical biology & medicine》2012,52(2):527-536
Although indolone-N-oxide (INODs) genereting long-lived radicals possess antiplasmodial activity in the low-nanomolar range, little is known about their mechanism of action. To explore the molecular basis of INOD activity, we screened for changes in INOD-treated malaria-infected erythrocytes (Pf-RBCs) using a proteomics approach. At early parasite maturation stages, treatment with INODs at their IC(50) concentrations induced a marked tyrosine phosphorylation of the erythrocyte membrane protein band 3, whereas no effect was observed in control RBCs. After INOD treatment of Pf-RBCs we also observed: (i) accelerated formation of membrane aggregates containing hyperphosphorylated band 3, Syk kinase, and denatured hemoglobin; (ii) dose-dependent release of microvesicles containing the membrane aggregates; (iii) reduction in band 3 phosphorylation, Pf-RBC vesiculation, and antimalarial effect of INODs upon addition of Syk kinase inhibitors; and (iv) correlation between the IC(50) and the INOD concentrations required to induce band 3 phosphorylation and vesiculation. Together with previous data demonstrating that tyrosine phosphorylation of oxidized band 3 promotes its dissociation from the cytoskeleton, these results suggest that INODs cause a profound destabilization of the Pf-RBC membrane through a mechanism apparently triggered by the activation of a redox signaling pathway rather than direct oxidative damage. 相似文献
56.
Victoria S. Haritos Hany Ghabrial Jorma T. Ahokas Michael S. Ching 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1999,736(1-2)
A stereoselective method of analysis of the antidepressant drug doxepin (DOX, an 85:15% mixture of E–Z stereoisomers), its principal metabolites E- and Z-N-desmethyldoxepin (desDOX) and ring-hydroxylated metabolites in microsomal incubation mixtures is described. DOX and its metabolites were extracted from alkalinised incubation mixtures by either: 9:1 hexane–propan-2-ol (method 1) or 1:1 hexane–dichloromethane (method 2), derivatised with trifluoroacetic anhydride and analysed by GC–MS with selected ion monitoring. Both methods were suitable for the analysis of individual desDOX isomers as indicated by correlation coefficients of ≥0.999 for calibration curves constructed between 50 and 2500 nM, and good within-day precision at 125 nM (C.V. ≤14%) and 1000 nM (C.V. ≤8%). Method 1, however, was unsuitable for the analysis of ring-hydroxylated metabolites of DOX, whereas the hydroxylated metabolites of E-DOX and E-desDOX (generated in situ) were extracted by method 2 with a C.V. of ca. 13%. This is the first assay method that permits the simultaneous measurement of desDOX and hydroxylated metabolites of DOX in microsomal mixtures. 相似文献
57.
58.
Hany E. A. Ahmed Mohammed A. A. El-Nassag Ahmed H. Hassan Rawda M. Okasha Saleh Ihmaid Ahmed M. Fouda 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):1074-1088
In our effort to develop novel and powerful agents with anti-proliferative activity, two new series of 1H-benzo[f]chromene derivatives, 4a–h and 6a–h, were synthesised using heterocyclocondensation methodologies under microwave irradiation condition. The structures of the target compounds were established on the basis of their spectral data, IR, 1H NMR, 13?C NMR, 13?C NMR-DEPT/APT, and MS data. The new compounds have been examined for their anti-proliferative activity against three cancer cell lines, MCF-7, HCT-116, and HepG-2. Vinblastine and Doxorubicin have been used as positive controls in the viability assay. The obtained results confirmed that most of the tested molecules revealed strong and selective cytotoxic activity against the three cancer cell lines. Moreover, these molecules exhibited weak cytotoxicity on the HFL-1?line, which suggested that they might be ideal anticancer candidates. The SAR study of the new benzochromene compounds verified that the substituents on the phenyl ring of 1H-benzo[f]chromene nucleus, accompanied with the presence of bromine atom or methoxy group at the 8-position, increases the ability of these molecules against the different cell lines. Due to their high anti-proliferative activity, compounds 4c and 6e were selected to be examined their proficiency to inhibit the invasiveness of the highly sensitive and invasive breast cancer cell line, MDA-MB-231. The anti-invasion behaviour of these molecules against the highly sensitive, non-oestrogen, and progesterone MDA-MB-231 cell line gave rise to their decreasing metastatic effect compared to the reference drug. Furthermore, this report explores the apoptotic mechanistic pathway of the cytotoxicity of the target compounds and reveals that most of these compounds enhance the Caspase 3/7 activity that could be considered as potential anticancer agents. 相似文献
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