SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL DISPIRO COMPOUNDS BASED ON 5-ARYLIDENEHYDANTOINS AND ISATINS AS INHIBITORS OF P53–MDM2 PROTEIN–PROTEIN INTERACTION

Authors

  • Anastasia Beloglazkina Lomonosov Moscow State University, 1 Build. 3 Leninskie Gory, Moscow 119991, Russia
  • Alexander Barashkin Lomonosov Moscow State University, 1 Build. 3 Leninskie Gory, Moscow 119991, Russia
  • Vladislav Polyakov Lomonosov Moscow State University, 1 Build. 3 Leninskie Gory, Moscow 119991, Russia
  • German Kotovsky Lomonosov Moscow State University, 1 Build. 3 Leninskie Gory, Moscow 119991, Russia
  • Nikita Karpov Lomonosov Moscow State University, 1 Build. 3 Leninskie Gory, Moscow 119991, Russia
  • Sofia Mefedova Lomonosov Moscow State University, 1 Build. 3 Leninskie Gory, Moscow 119991, Russia
  • Bogdan Zagribelny Lomonosov Moscow State University, 1 Build. 3 Leninskie Gory, Moscow 119991, Russia Moscow Institute of Physics and Technology (State University), 9 Institutskiy Pereulok, Dolgoprudny 141700, Moscow Region, Russia
  • Yan Ivanenkov Moscow Institute of Physics and Technology (State University), 9 Institutskiy Pereulok, Dolgoprudny 141700, Moscow Region, Russia
  • Marina Kalinina Skolkovo Institute of Science and Technology, 4 Alfred Nobel St., Skolkovo 143025, Russia
  • Dmitry Skvortsov Lomonosov Moscow State University, 1 Build. 3 Leninskie Gory, Moscow 119991, Russia Faculty of Biology and Biotechnologies, Higher School of Economics, 7 Vavilova St., Moscow 117312, Russia
  • Victor Tafeenko Lomonosov Moscow State University, 1 Build. 3 Leninskie Gory, Moscow 119991, Russia
  • Nikolay Zyk Lomonosov Moscow State University, 1 Build. 3 Leninskie Gory, Moscow 119991, Russia
  • Alexander Majouga Lomonosov Moscow State University, 1 Build. 3 Leninskie Gory, Moscow 119991, Russia National University of Science and Technology MISiS, 9 Leninsky Ave., Moscow 119049, Russia D. Mendeleev University of Chemical Technology of Russia, 9 Miusskaya Sq., Moscow 125047, Russia
  • Elena Beloglazkina Lomonosov Moscow State University, 1 Build. 3 Leninskie Gory, Moscow 119991, Russia

DOI:

https://doi.org/10.1007/5613

Keywords:

hydantoins, spirooxindole, anticancer drugs, 1, 3-dipolar cycloaddition, p53–MDM2 inhibitors.

Abstract

A series of novel hydantoin-based dispiroindolinones as potential small-molecule inhibitors of p53–MDM2 protein–protein interaction were synthesized by two methods, using 2-arylidenehydantoins as starting materials. Some compounds demonstrate moderate cytotoxicity against cancer cell lines with IC50 in micromolar concentration range, which is comparable to nutlin-3. Two of the synthesized dispiroindolinones show p53-related activity in p53 reporter activation test.

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Published

2020-07-10

Issue

Vol. 56 No. 6 (2020): Heterocyclic сompounds in medicinal chemistry

Section

Original Papers