title: Antiproliferative diarylpyrazole derivatives as dual inhibitors of the ERK pathway and COX-2.
abstract: 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 National Cancer Institute (NCI, Bethesda, MD, USA) at a single-dose concentration of 10 μm, and the four most active compounds 9a, 9l, 9n, and 10o were further tested in a five-dose testing mode to determine their IC50 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.
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul, 130-650, Korea; Department of Biomolecular Science, University of Science and Technology, 113 Gwahangno, Yuseong-gu, Daejeon, 305-333, Korea; Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura, 35516, Egypt.
authors.forename: Mohammed I
authors.initials: MI
authors.lastname: El-Gamal
authors.forename: Hong Seok
authors.initials: HS
authors.lastname: Choi
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Yoo
authors.forename: Daejin
authors.initials: D
authors.lastname: Baek
authors.forename: Chang-Hyun
authors.initials: CH
authors.lastname: Oh
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000737:chemistry* / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases
keywords: 3,4-diarylpyrazole-1-carboxamide; ERK pathway; anticancer; cyclooxygenase-2; pyrazole; vicinal diaryl heterocycle