ABSTRACT
A series of new pyrimidine-pyrazole hybrid molecules were designed as inhibitors of cyclin-dependent kinase 2. Designed compounds were docked using Glide and the compounds showing good score values and encouraging interactions with the residues were selected for synthesis. They were then evaluated using CDK2-CyclinA2 enzyme inhibition by a luminescent ADP detection assay. We show that of the 26 compounds synthesized and evaluated, at least 5 compounds were found to be highly potent (IC50 < 20 nm); which can be further optimized to have selectivity over other kinase isoforms.
Subject(s)
Cyclin-Dependent Kinase 2/antagonists & inhibitors , Drug Design , Protein Kinase Inhibitors/chemical synthesis , Pyrazoles/chemistry , Pyrimidines/chemistry , Binding Sites , Cyclin-Dependent Kinase 2/metabolism , Humans , Inhibitory Concentration 50 , Molecular Docking Simulation , Protein Isoforms/antagonists & inhibitors , Protein Isoforms/metabolism , Protein Kinase Inhibitors/metabolism , Protein Structure, Tertiary , Pyrazoles/metabolism , Structure-Activity RelationshipABSTRACT
Adsorption of lead (II) ions onto cassava starch 5-choloromethyl-8-hydroxyquinoline polymer (CSCMQ) was investigated with the variation in the parameters of pH, contact time, lead (II) ions concentration, temperature and the adsorbent dose. The Langmuir and Freundlich models have been applied. CSCMQ was characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. Results showed that the adsorption process was better described by the Langmuir model. Adsorption kinetics data obtained for the metal ions sorption were investigated using pseudo-first-order, pseudo-second-order and intraparticle diffusion model. The maximum adsorption capacities (qm) were 46.512, 43.859 and 42.735 mg/g at 25, 35 and 45 °C, respectively. The dynamical data fit well with the second-order kinetics model. The results indicate that CSCMQ could be employed as low-cost material for the adsorption of Pb(II) ions from aqueous medium.
