New diarylureas and diarylamides containing 1,3,4-triarylpyrazole scaffold: Synthesis, antiproliferative evaluation against melanoma cell lines, ERK kinase inhibition, and molecular docking studies
| Autor: | Won-Kyoung Choi, Chang-Hyun Oh, Mohammed I. El-Gamal, Daejin Baek, Hong Seok Choi |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular Proto-Oncogene Proteins B-raf Scaffold MAP Kinase Signaling System Antineoplastic Agents Structure-Activity Relationship Cell Line Tumor Drug Discovery medicine Humans Structure–activity relationship Potency Melanoma Protein Kinase Inhibitors Cell Proliferation Pharmacology Virtual screening Chemistry Organic Chemistry General Medicine medicine.disease In vitro Biochemistry Docking (molecular) Cell culture Pyrazoles Drug Screening Assays Antitumor |
| Zdroj: | European Journal of Medicinal Chemistry. 46:5754-5762 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2011.08.013 |
| Popis: | Synthesis of a new series of diarylureas and diarylamides possessing 1,3,4-triarylpyrazole scaffold is described. Their in vitro antiproliferative activities against 9 human melanoma cell lines were tested. Compounds 12, 13, 15, and 21-23 showed the highest potency against A375P melanoma cell line. In addition, compounds 10-15 and 19-24 showed high potency over the NCI 8 tested melanoma cell-lines panel. The IC(50) values for compound 23 were 0.36 μM and 0.84 μM over LOX IMVI and M14 cell lines, respectively. Compounds 21 and 23 showed high, dose-dependent inhibition of ERK kinase. Virtual screening was carried out through docking of compound 21 into the domain of V600E-B-RAF and the binding mode was studied. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect