title: Design, synthesis and biological evaluation of novel potent MDM2/p53 small-molecule inhibitors.
abstract: Regioselective synthesis, biological evaluation and 3D-molecular modeling for a series of novel diastereomeric 2-thioxo-5H-dispiro[imidazolidine-4,3-pyrrolidine-2,3-indole]-2,5(1H)-diones are described. The studied compounds have been tentatively identified as potent small molecule MDM2/p53 PPI inhibitors and can therefore be reasonably regarded as promising anticancer therapeutics.
authors.affiliation: ChemDiv, Inc., 6605 Nancy Ridge Drive, San Diego, CA 92121, USA; Moscow Institute of Physics and Technology (MIPT), Dolgoprudny, InstitutskiPereulok 9, Moskovskaya Oblast, Russia; Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, 119991 Moscow, Russia. Electronic address: yai@chemdiv.com.
authors.forename: Yan A
authors.initials: YA
authors.lastname: Ivanenkov
authors.affiliation: Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, 119991 Moscow, Russia.
authors.forename: Sergei V
authors.initials: SV
authors.lastname: Vasilevski
authors.affiliation: Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, 119991 Moscow, Russia; Moscow State University of Mechanical Engineering (MAMI), Moscow, Russia.
authors.forename: Elena K
authors.initials: EK
authors.lastname: Beloglazkina
authors.affiliation: Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, 119991 Moscow, Russia.
authors.forename: Maksim E
authors.initials: ME
authors.lastname: Kukushkin
authors.affiliation: Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, 119991 Moscow, Russia; Moscow State University of Mechanical Engineering (MAMI), Moscow, Russia.
authors.forename: Alexey E
authors.initials: AE
authors.lastname: Machulkin
authors.affiliation: Moscow Institute of Physics and Technology (MIPT), Dolgoprudny, InstitutskiPereulok 9, Moskovskaya Oblast, Russia. Electronic address: vms@pharmcluster.ru.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Veselov
authors.affiliation: Moscow Institute of Physics and Technology (MIPT), Dolgoprudny, InstitutskiPereulok 9, Moskovskaya Oblast, Russia; National University of Science and Technology MISiS, Moscow 119049, Russia.
authors.forename: Nina V
authors.initials: NV
authors.lastname: Chufarova
authors.affiliation: Moscow Institute of Physics and Technology (MIPT), Dolgoprudny, InstitutskiPereulok 9, Moskovskaya Oblast, Russia.
authors.forename: Elizaveta S
authors.initials: ES
authors.lastname: Chernyaginab
authors.affiliation: ChemDiv, Inc., 6605 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Anton S
authors.initials: AS
authors.lastname: Vanzcool
authors.affiliation: Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, 119991 Moscow, Russia.
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Zyk
authors.affiliation: Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, 119991 Moscow, Russia.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Skvortsov
authors.affiliation: Belozersky Institute, Lomonosov Moscow State University, Leninskie Gory, 1/40, 119992, Moscow, Russia.
authors.forename: Anastasia A
authors.initials: AA
authors.lastname: Khutornenko
authors.affiliation: Moscow State University of Mechanical Engineering (MAMI), Moscow, Russia.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Rusanov
authors.affiliation: SRC Bioclinicum, Ugreshskaya str 2/85, Moscow 115088, Russia; P.A. Hertsen Moscow Research Oncology Institute, 2nd Botkinsky st., 125284 Moscow, Russia.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Tonevitsky
authors.affiliation: Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, 119991 Moscow, Russia; Belozersky Institute, Lomonosov Moscow State University, Leninskie Gory, 1/40, 119992, Moscow, Russia.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Dontsova
authors.affiliation: Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, 119991 Moscow, Russia; National University of Science and Technology MISiS, Moscow 119049, Russia. Electronic address: majouga@org.chem.msu.ru.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Majouga
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D054852:Small Molecule Libraries; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: 3D molecular docking; Cell-based assay; Dispiro-indolinones; MDM2/p53; PPI inhibitors