Novel hydrazide-hydrazone and amide substituted coumarin derivatives: Synthesis, cytotoxicity screening, microarray, radiolabeling and in vivo pharmacokinetic studies
Date
2018
Journal Title
Journal ISSN
Volume Title
Type
Article
Publisher
Pharmacologyonline
Elsevier Masson SAS
Elsevier Masson SAS
Series Info
European Journal of Medicinal Chemistry
151
151
Scientific Journal Rankings
Abstract
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
Description
Scopus
MSA Google Scholar
MSA Google Scholar
Keywords
October University for Modern Sciences and Arts, جامعة أكتوبر للعلوم الحديثة والآداب, University of Modern Sciences and Arts, MSA University, Apoptosis, Caspases 3/7, Coumarin hydrazide-hydrazone, CYP3A4, GST, Microarray, Radiolabeling, 2 chloro 6 ethoxy 3 formylquinoline, 2 oxo n' [(pyridin 3 yl)methylene] 2h chromene 3 carbohydrazide, 2 oxo n' [(pyridin 4 yl)methylene] 2h chromene 3 carbohydrazide, 6 bromo 2 oxo n' [(pyridin 3 yl)methylene] 2h chromene 3 carbohydrazide, 6 bromo 2 oxo n' [(pyridin 4 yl)methylene] 2h chromene 3 carbohydrazide, 6 bromo n (4 ethoxyphenyl) 2 oxo 2h chromene 3 carboxamide, 6 bromo n' [(2 chloro 6 ethoxyquinolin 3 yl)methylene] 2 oxo 2h chromene 3 carbohydrazide, 6 nitro 2 oxo n' [(pyridin 3 yl)methylene] 2h chromene 3 carbohydrazide, 6 nitro 2 oxo n' [(pyridin 4 yl)methylene] 2h chromene 3 carbohydrazide, 7 hydroxy 2 oxo n' [(pyridin 3 yl)methylene] 2h chromene 3 carbohydrazide, amide, antineoplastic agent, caspase 3, caspase 7, coumarin derivative, cytochrome P450 3A4, doxorubicin, hydrazide derivative, hydrazone derivative, n (4 ethoxyphenyl) 2 oxo 2h chromene 3 carboxamide, n (4 ethoxyphenyl) 6 nitro 2 oxo 2h chromene 3 carboxamide, n (4 ethoxyphenyl) 7 hydroxy 2 oxo 2h chromene 3 carboxamide, n (4 {[(3,4 dimethylisoxazol 4 yl)amino]sulfonyl}phenyl) 2 oxo chromene 3 carboxamide, n (4 {[(3,4 dimethylisoxazol 4 yl)amino]sulfonyl}phenyl) 6 bromo 2 oxo chromene 3 carboxamide, n (4 {[(3,4 dimethylisoxazol 4 yl)amino]sulfonyl}phenyl) 6 nitro 2 oxo chromene 3 carboxamide, n' [(2 chloro 6 ethoxyquinolin 3 yl)methylene] 2 cyanoacetohydrazide, n' [(2 chloro 6 ethoxyquinolin 3 yl)methylene] 2 oxo 2h chromene 3 carbohydrazide, n' [(2 chloro 6 ethoxyquinolin 3 yl)methylene] 6 nitro 2 oxo 2h chromene 3 carbohydrazide, n' [(2 chloro 6 ethoxyquinolin 3 yl)methylene] 7 hydroxy 2 oxo 2h chromene 3 carbohydrazide, unclassified drug, unindexed drug, antineoplastic agent, coumarin derivative, cytochrome P450 3A, cytochrome P450 3A inhibitor, hydrazone derivative, antiproliferative activity, apoptosis, Article, cell cycle, controlled study, down regulation, drug bioavailability, drug cytotoxicity, drug screening, drug synthesis, enzyme activation, enzyme assay, Hep-G2 cell line, human, human cell, in vitro study, in vivo study, isotope labeling, Knoevenagel condensation, leukemia, liver cell carcinoma, metabolic inhibition, microarray analysis, PANC-1 cell line, pancreas carcinoma, pharmacokinetic parameters, proton nuclear magnetic resonance, structure activity relation, tumor growth, tumor suppressor gene, upregulation, animal, chemistry, drug effect, halogenation, metabolism, mouse, neoplasm, pathology, synthesis, tissue distribution, tumor cell line, Animals, Antineoplastic Agents, Apoptosis, Cell Line, Tumor, Coumarins, Cytochrome P-450 CYP3A, Cytochrome P-450 CYP3A Inhibitors, Halogenation, Humans, Hydrazones, Mice, Neoplasms, Tissue Distribution