Browsing by Author "Rashed H.M."

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In silico-based repositioning of phosphinothricin as a novel technetium-99m imaging probe with potential anti-cancer activity
(MDPI AG, 2018) Sakr T.M.; Khedr M.A.; Rashed H.M.; Mohamed M.E.; Radioactive Isotopes and Generator Department; Hot Labs Center; Atomic Energy Authority; Cairo; 13759; Egypt; Pharmaceutical Chemistry Department; Faculty of Pharmacy; October University of Modern Sciences and Arts (MSA); Giza; 12111; Egypt; Department of Pharmaceutical Chemistry; Faculty of Pharmacy; Helwan University; Ein Helwan; Cairo; 11795; Egypt; College of Clinical Pharmacy; King Faisal University; Al-Hasaa; 31982; Saudi Arabia; Labeled Compounds Department; Hot Labs Center; Atomic Energy Authority; Cairo; 13759; Egypt; Department of Pharmacognosy; Faculty of Pharmacy; University of Zagazig; Zagazig; 44519; Egypt
L-Phosphinothricin (glufosinate or 2-amino-4-((hydroxy(methyl) phosphinyl) butyric acid ammonium salt (AHPB)), which is a structural analog of glutamate, is a recognized herbicide that acts on weeds through inhibition of glutamine synthetase. Due to the structural similarity between phosphinothricin and some bisphosphonates (BPs), this study focuses on investigating the possibility of repurposing phosphinothricin as a bisphosphonate analogue, particularly in two medicine-related activities: image probing and as an anti-cancer drug. As BP is a competitive inhibitor of human farnesyl pyrophosphate synthase (HFPPS), in silico molecular docking and dynamic simulations studies were established to evaluate the binding and stability of phosphinothricin with HFPPS, while the results showed good binding and stability in the active site of the enzyme in relation to alendronate. For the purpose of inspecting bone-tissue accumulation of phosphinothricin, a technetium (99mTc)�phosphinothricin complex was developed and its stability and tissue distribution were scrutinized. The radioactive complex showed rapid, high and sustained uptake into bone tissues. Finally, the cytotoxic activity of phosphinothricin was tested against breast and lung cancer cells, with the results indicating cytotoxic activity in relation to alendronate. All the above results provide support for the use of phosphinothricin as a potential anti-cancer drug and of its technetium complex as an imaging probe. � 2018 by the authors.
Novel hydrazide-hydrazone and amide substituted coumarin derivatives: Synthesis, cytotoxicity screening, microarray, radiolabeling and in vivo pharmacokinetic studies
(Pharmacologyonline, 2018) Nasr T.; Bondock S.; Rashed H.M.; Fayad W.; Youns M.; Sakr T.M.; Department of Pharmaceutical Chemistry; Faculty of Pharmacy; Helwan University; Egypt; Department of Pharmaceutical Chemistry; Faculty of Pharmacy; Modern University for Technology and Information; Egypt; Department of Chemistry; Faculty of Science; Mansoura University; Mansoura; ET-35516; Egypt; Department of Chemistry; Faculty of Science; King Khalid University; Abha; 9004; Saudi Arabia; Labeled Compounds Department; Hot Labs Center; Egyptian Atomic Energy Authority; P.O. Code 13759; Cairo; Egypt; Drug Bioassay-Cell Culture Laboratory; Pharmacognosy Department; National Research Centre; Dokki; Giza 12622; Egypt; Department of Biochemistry and Molecularlar Biology; Faculty of Pharmacy; Helwan University; Egypt; Radioactive Isotopes and Generators Department; Hot Laboratories Centre; Atomic Energy Authority; P.O. Code 13759; Cairo; Egypt; Pharmaceutical Chemistry Department; Faculty of Pharmacy; October University of Modern Sciences and Arts (MSA)Giza; Egypt
The current work presents the synthesis and biological evaluation of new series of coumarin hydrazide-hydrazone derivatives that showed in vitro broad spectrum antitumor activities against resistant pancreatic carcinoma (Panc-1), hepatocellular carcinoma (HepG2) and leukemia (CCRF) cell lines using doxorubicin as reference standard. Bromocoumarin hydrazide-hydrazone derivative (BCHHD) 11b showed excellent anticancer activity against all tested cancer cell lines. Enzyme assays showed that BCHHD 11b induced apoptosis due to activation of caspases 3/7. Moreover, 11b inhibited GST and CYP3A4 in a dose dependent manner and the induced cell death could be attributed to metabolic inhibition. Moreover, 11b microarray analysis showed significant up- and down-regulation of many genes in the treated cells related to apoptosis, cell cycle, tumor growth and suppressor genes. All of the above presents BCHHD 11b as a potent anticancer agent able to overcome drug resistance. In addition, compound 11b was able to serve as a chemical carrier for 99mTc and the in vivo biodistribution study of 99mTc-11b complex revealed a remarkable targeting ability of 99mTc into solid tumor showing that 99mTc-11b might be used as a promising radiopharmaceutical imaging agent for cancer. � 2018 Elsevier Masson SAS
Preparation and biological profile of 99mTc-lidocaine as a cardioselective imaging agent using 99mTc eluted from 99Mo/99mTc generator based on AlMo gel
(Springer Netherlands, 2017) Sakr T.M.; Ibrahim A.B.; Fasih T.W.; Rashed H.M.; Radioactive Isotopes and Generators Department; Hot Laboratories Centre; Atomic Energy Authority; Cairo; 13759; Egypt; Pharmaceutical Chemistry Department; Faculty of Pharmacy; October University of Modern Sciences and Arts (MSA); Giza; Egypt; Labeled Compounds Department; Hot Labs Center; Atomic Energy Authority; P.O. Box 13759; Cairo; Egypt
The current study is aimed to prepare 99mTc-lidocaine as a new myocardial perfusion-imaging agent. The used 99mTc was obtained from Al. 99Mo-molybdate(VI) gel matrix. 99mTc-lidocaine showed higher (15.4. 0.11% ID/g) and faster (15. min post injection) cardiac uptake than the recently studied 99mTc-valsartan and 99mTc-procainamide. Consequently, 99mTc-lidocaine will be a valuable myocardial SPECT agent for diagnosis of emergency patients. Besides, the receptor affinity study confirmed the selectivity of 99mTc-lidocaine for sodium channels in the heart. 2017, Akadmiai Kiad, Budapest, Hungary.