title: Pyrrolo[2,3-a]carbazoles as potential cyclin dependent kinase 1 (CDK1) Inhibitors. Synthesis, biological evaluation, and binding mode through docking simulations.
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.
authors.affiliation: Laboratory of Medicinal Chemistry, Department of Pharmacy, School of Health Sciences, University of Patras, GR-26500 Rion, Patras, Greece.
authors.forename: Manolis A
authors.initials: MA
authors.lastname: Fousteris
authors.forename: Athanasios
authors.initials: A
authors.lastname: Papakyriakou
authors.forename: Anna
authors.initials: A
authors.lastname: Koutsourea
authors.forename: Maria
authors.initials: M
authors.lastname: Manioudaki
authors.forename: Evgenia
authors.initials: E
authors.lastname: Lampropoulou
authors.forename: Evangelia
authors.initials: E
authors.lastname: Papadimitriou
authors.forename: Georgios A
authors.initials: GA
authors.lastname: Spyroulias
authors.forename: Sotiris S
authors.initials: SS
authors.lastname: Nikolaropoulos
mesh_terms: D001665:Binding Sites; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D002227:Carbazoles; D011758:Pyrroles; D016203:CDC2 Protein Kinase