16036-15-0Relevant articles and documents
Synthesis and selective inhibitory effects of some 2-oxindole benzenesulfonamide conjugates on human carbonic anhydrase isoforms CA I, CA II, CA IX and CAXII
George, Riham F.,Said, Mona F.,Bua, Silvia,Supuran, Claudiu T.
, (2020)
Three series of 2-oxindole benzenesulfonamide conjugates with different linkers were prepared by the condensation reaction of isatin derivatives 1a-e with different benzenesulfonamides. They were screened for their ability to inhibit human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, hCA II, hCA IX and hCA XII. Many compounds revealed promising activity and selectivity toward CAI, CAII and CAIX compared to acetazolamide (AAZ) especially compounds 2b (KI = 97.6, 8.0 nM against hCA I, hCA II, respectively) and 3a (KI = 90.2, 6.5 and 21.4 nM against hCA I, hCA II and hCA IX, respectively) relative to AAZ (KI = 250, 12 and 25 nM). Additionally, compound 4a revealed the highest activity against hCA II and hCA IX with KI of 3.0 and 13.9 nM, respectively. Docking of 2b, 3a and 4a into the active site of CA I, II, IX and XII revealed binding mode comparable to AAZ confirming the inhibition results.
Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): Design, synthesis, enzymatic activities, and X-ray crystallographic analysis
Bramson,Holmes,Hunter,Lackey,Lovejoy,Luzzio,Montana,Rocque,Rusnak,Shewchuk,Veal,Corona,Walker,Kuyper,Davis,Dickerson,Edelstein,Frye,Gampe Jr.,Harris,Hassell
, p. 4339 - 4358 (2007/10/03)
Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). The initial lead compound was prepared as a homologue of the 3-benzylidene-1,3-dihydro-2H-indol-2-one class of kinase inhibitor. Crystallographic analysis of the lead compound bound to CDK2 provided the basis for analogue design. A semiautomated method of ligand docking was used to select compounds for synthesis, and a number of compounds with low nanomolar inhibitory activity versus CDK2 were identified. Enzyme binding determinants for several analogues were evaluated by X-ray crystallography. Compounds in this series inhibited CDK2 with a potency ～10-fold greater than that for CDK1. Members of this class of inhibitor cause an arrest of the cell cycle and have shown potential utility in the prevention of chemotherapy-induced alopecia.
