Design, synthesis and evaluation of (E)-alpha-benzylthio chalcones as novel inhibitors of BCR-ABL kinase.
Novel (E)-alpha-benzylthio chalcones are reported with preliminary in vitro activity data indicating that several of them are potent inhibitors (comparable to imatinib, the reference compound) of BCR-ABL phosphorylation in leukemic K562 cells, known to express high levels of BCR-ABL. The ability of such compounds to significantly inhibit K562 cell proliferation suggests that this scaffold could be a promising lead for the development of anticancer agents that are able to block BCR-ABL phosphorylation in leukemic cells.
Reddy
M V Ramana
MVR
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, PA 19140-5101, United States.
Pallela
Venkat R
VR
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, PA 19140-5101, United States.
Cosenza
Stephen C
SC
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, PA 19140-5101, United States.
Mallireddigari
Muralidhar R
MR
Onconova Therapeutics Inc., 375 Pheasant Run, Newtown, PA 18940, United States.
Patti
Revathi
R
Onconova Therapeutics Inc., 375 Pheasant Run, Newtown, PA 18940, United States.
Bonagura
Marie
M
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, PA 19140-5101, United States.
Truongcao
May
M
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, PA 19140-5101, United States.
Akula
Balaiah
B
Onconova Therapeutics Inc., 375 Pheasant Run, Newtown, PA 18940, United States.
Jatiani
Shashidhar S
SS
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, PA 19140-5101, United States.
Reddy
E Premkumar
EP
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, PA 19140-5101, United States.
D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D015394:Molecular Structure; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
C549755:(E)-alpha-benzylthio chalcone; D047188:Chalcones; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl