Browsing by Author "Nasr T."

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    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