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Antiproliferative Diarylpyrazole Derivatives as Dual Inhibitors of the ERK Pathway and COX ‐2
Author(s) -
ElGamal Mohammed I.,
Choi Hong Seok,
Yoo Kyung Ho,
Baek Daejin,
Oh ChangHyun
Publication year - 2013
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12186
Subject(s) - mapk/erk pathway , cyclooxygenase , chemistry , kinase , cell culture , western blot , inhibitory postsynaptic potential , in vitro , isozyme , pharmacology , enzyme , biochemistry , microbiology and biotechnology , biology , genetics , neuroscience , gene
A series of 3,4‐diarylpyrazole‐1‐carboxamide derivatives was designed and synthesized. A selected group of the target compounds was tested for in vitro antiproliferative activities over a panel of 60 cancer cell lines at the N ational C ancer I nstitute ( NCI , B ethesda, MD , USA ) at a single‐dose concentration of 10 μ m , and the four most active compounds 9a , 9l , 9n , and 10o were further tested in a five‐dose testing mode to determine their IC 50 values over the 60 cell lines. In addition, a selected group of target compounds were tested for inhibitory effect over cyclooxygenase isozymes. Compounds 9a , 9l , 9n , and 10o were also tested for MEK and ERK kinase inhibitory activity using Western blot assay. Compound 10o was selective toward melanoma cell line subpanel, and its antiproliferative activity may be attributed to selective cyclooxygenase‐2 inhibition and ERK pathway inhibition.