Molecules, Vol. 25, Pages 2135: Phenylpyrazalopyrimidines as Tyrosine Kinase Inhibitors: Synthesis, Antiproliferative Activity, and Molecular Simulations

Molecules, Vol. 25, Pages 2135: Phenylpyrazalopyrimidines as Tyrosine Kinase Inhibitors: Synthesis, Antiproliferative Activity, and Molecular Simulations Molecules doi: 10.3390/molecules25092135 Authors: Bhupender S. Chhikara Sajda Ashraf Saghar Mozaffari Nicole St. Jeans Dindyal Mandal Rakesh Kumar Tiwari Zaheer Ul-Haq Keykavous Parang N1-(α,β-Alkene)-substituted phenylpyrazolopyrimidine derivatives with acetyl and functionalized phenyl groups at α- and β-positions, respectively, were synthesized by the reaction of 3-phenylpyrazolopyrimidine (PhPP) with bromoacetone, followed by a chalcone reaction with differently substituted aromatic aldehydes. The Src kinase enzyme assay revealed modest inhibitory activity (half maximal inhibitory concentration, IC50 = 21.7–192.1 µM) by a number of PhPP derivatives. Antiproliferative activity of the compounds was evaluated on human leukemia (CCRF-CEM), human ovarian adenocarcinoma (SK-OV-3), breast carcinoma (MDA-MB-231), and colon adenocarcinoma (HT-29) cells in vitro. 4-Chlorophenyl carbo-enyl substituted 3-phenylpyrazolopyrimidine (10) inhibited the cell proliferation of HT-29 and SK-OV-3 by 90% and 79%, respectively, at a concentration of 50 µM after 96 h incubation. The compound showed modest inhibitory activity against c-Src (IC50 = 60.4 µM), Btk (IC50 = 90.5 µM), and Lck (IC50 = 110 &...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research