Pyrrolo[2,3-a]carbazoles as potential cyclin dependent kinase 1 (CDK1) Inhibitors. Synthesis, biological evaluation, and binding mode through docking simulations.

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Fousteris MA, Papakyriakou A, Koutsourea A, Manioudaki M, Lampropoulou E, Papadimitriou E, Spyroulias GA, Nikolaropoulos SS

Pyrrolo[2,3-a]carbazoles as potential cyclin dependent kinase 1 (CDK1) Inhibitors. Synthesis, biological evaluation, and binding mode through docking simulations.

J Med Chem. 2008 Feb 28;51(4):1048-52. doi: 10.1021/jm0700666. Epub 2008 Jan 31.

PubMed ID

18232654 [ View in PubMed

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Abstract

Pyrrolo[2,3- a]carbazole derivatives were synthesized, and their effects on CDK1/cyclinB activity were evaluated. The most potent and efficacious inhibitor was found to be ethyl 9-chloro-1H-pyrrolo[2,3-alpha]carbazole-2-carboxylate (1e), exhibiting an IC50 in the low micromolar range and leading to 90% at higher concentrations. Using a computational model for CDK1-1e, binding we have observed that 1e exhibited two likely binding modes in the ATP-binding cleft that involve interactions with Lys130, Thr14, and Asp146 of the enzyme.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Olomoucine	Cyclin-dependent kinase 1	IC 50 (nM)	7000	N/A	N/A	Details