title: 2,30-Bis(10H-indole) heterocycles: New p53/MDM2/MDMX antagonists.
abstract: The protein–protein interaction of p53 and MDM2/X is a promising non genotoxic anticancer target. A rapid and efficient methodology was developed to synthesize the 2,30-bis(10H-indole) heterocyclic scaffold 2 as ester, acid and amide derivatives. Their binding affinity with MDM2 was evaluated using both fluorescence polarization (FP) assay and HSQC experiments, indicating good inhibition and a perfect starting point for further optimizations.
authors.affiliation: Department of Drug Design, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands
authors.forename: Constantinos G
authors.initials: CG
authors.lastname: Neochoritis
authors.forename: Kan
authors.initials: K
authors.lastname: Wang
authors.forename: Natalia
authors.initials: N
authors.lastname: Estrada-Ortiz
authors.forename: Eberhardt
authors.initials: E
authors.lastname: Herdtweck
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kubica
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Twarda
authors.forename: Krzysztof M
authors.initials: KM
authors.lastname: Zak
authors.forename: Tad A
authors.initials: TA
authors.lastname: Holak
authors.forename: Alexander
authors.initials: A
authors.lastname: Dömling
mesh_terms: D001665:Binding Sites; D005454:Fluorescence Polarization; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D007211:Indoles / Q000737:chemistry; D062105:Molecular Docking Simulation; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D006571:Heterocyclic Compounds; D007211:Indoles; D016159:Tumor Suppressor Protein p53; C030374:indole; D051736:Proto-Oncogene Proteins c-mdm2