Premium
Design, Synthesis, and Antiproliferative Activity of 3,4‐Diarylpyrazole‐1‐carboxamide Derivatives Against Melanoma Cell Line
Author(s) -
ElGamal Mohammed I.,
Choi Hong Seok,
Cho HaeGuk,
Hong Jun Hee,
Yoo Kyung Ho,
Oh ChangHyun
Publication year - 2011
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201000375
Subject(s) - carboxamide , chemistry , sorafenib , cell culture , melanoma , stereochemistry , biological activity , docking (animal) , chemical synthesis , in vitro , biochemistry , cancer research , biology , medicine , hepatocellular carcinoma , genetics , nursing
Abstract Synthesis of a new series of 3,4‐diarylpyrazole‐1‐carboxamide derivatives is described. Their antiproliferative activity against A375P human melanoma cell line was tested and the effect of substituents on the diarylpyrazole scaffold was investigated. The biological results indicated that five synthesized compounds ( Ig , Ii , IIc , IIg , and IIh ) exhibited similar activity to Sorafenib. In addition, three compounds ( IIa , IIb , and IIi ) were more potent than Sorafenib. Among all of these derivatives, compound IIa which has dimethylamino and phenolic moieties showed the most potent antiproliferative activity against A375P human melanoma cell line. Virtual screening was carried out through docking of the most potent compound IIa into the domain of V600E‐b‐Raf and the binding mode was studied.