title: One-pot regioselective synthesis of tetrahydroindazolones and evaluation of their antiproliferative and Src kinase inhibitory activities.
abstract: A number of 2-substituted tetrahydroindazolones were synthesized by three-component condensation reaction of 1,3-diketones, substituted hydrazines, benzaldehydes, and Yb(OTf)(3) as a catalyst in [bmim][BF(4)] ionic liquid using a simple, efficient, and economical one-pot method. The synthesized tetrahydroindazolones were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), human ovarian adenocarcinoma (SK-OV-3), and c-Src kinase activity. 3,4-Dichlorophenyl tetrahydroindazolone derivative (15) inhibited the cell proliferation of HT-29 and SK-OV-3 cells by 62% and 58%, respectively. 2,3-Diphenylsubstituted tetrahydroindazolone derivatives, inhibited the cell proliferation of HT-29 cells by 65-72% at a concentration of 50 μM. In general, the tetrahydroindazolones showed modest inhibition of c-Src kinase where 4-tertbutylphenyl- and 3,4-dichlorophenyl- derivatives showed the inhibition of c-Src kinase with IC(50) values of 35.1 and 50.7 μM, respectively.
authors: Department of Chemistry, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India.
authors: V Kameshwara
authors: VK
authors: Rao
authors: Bhupender S
authors: BS
authors: Chhikara
authors: Rakesh
authors: R
authors: Tiwari
authors: Amir Nasrolahi
authors: AN
authors: Shirazi
authors: Keykavous
authors: K
authors: Parang
authors: Anil
authors: A
authors: Kumar
mesh_terms: D002384:Catalysis; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D019073:HT29 Cells; D006801:Humans; D007191:Indazoles / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007477:Ions; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D019061:src-Family Kinases / Q000737:chemistry*
chemical_list: D007191:Indazoles; D007477:Ions; D019061:src-Family Kinases