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Design, synthesis and biological evaluation of novel potent MDM2/p53 small-molecule inhibitors.
Bioorg Med Chem Lett. 2015 Jan 15; 25(2):404-9.BM

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Ivanenkov YA
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.
Vasilevski SV
Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, 119991 Moscow, Russia.
Beloglazkina EK
Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, 119991 Moscow, Russia; Moscow State University of Mechanical Engineering (MAMI), Moscow, Russia.
Kukushkin ME
Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, 119991 Moscow, Russia.
Machulkin AE
Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, 119991 Moscow, Russia; Moscow State University of Mechanical Engineering (MAMI), Moscow, Russia.
Veselov MS
Moscow Institute of Physics and Technology (MIPT), Dolgoprudny, InstitutskiPereulok 9, Moskovskaya Oblast, Russia. Electronic address: vms@pharmcluster.ru.
Chufarova NV
Moscow Institute of Physics and Technology (MIPT), Dolgoprudny, InstitutskiPereulok 9, Moskovskaya Oblast, Russia; National University of Science and Technology MISiS, Moscow 119049, Russia.
Chernyaginab ES
Moscow Institute of Physics and Technology (MIPT), Dolgoprudny, InstitutskiPereulok 9, Moskovskaya Oblast, Russia.
Vanzcool AS
ChemDiv, Inc., 6605 Nancy Ridge Drive, San Diego, CA 92121, USA.
Zyk NV
Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, 119991 Moscow, Russia.
Skvortsov DA
Moscow State University, Chemistry Dept., Leninskie Gory, Building 1/3, GSP-1, 119991 Moscow, Russia.
Khutornenko AA
Belozersky Institute, Lomonosov Moscow State University, Leninskie Gory, 1/40, 119992, Moscow, Russia.
Rusanov AL
Moscow State University of Mechanical Engineering (MAMI), Moscow, Russia.
Tonevitsky AG
SRC Bioclinicum, Ugreshskaya str 2/85, Moscow 115088, Russia; P.A. Hertsen Moscow Research Oncology Institute, 2nd Botkinsky st., 125284 Moscow, Russia.
Dontsova OA
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.
Majouga AG
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.

MeSH

Antineoplastic AgentsCell ProliferationDrug DesignHumansModels, MolecularMolecular Dynamics SimulationMolecular StructureNeoplasmsProto-Oncogene Proteins c-mdm2Small Molecule LibrariesStructure-Activity RelationshipTumor Cells, CulturedTumor Suppressor Protein p53

Pub Type(s)

Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25479770

Citation

Ivanenkov, Yan A., et al. "Design, Synthesis and Biological Evaluation of Novel Potent MDM2/p53 Small-molecule Inhibitors." Bioorganic & Medicinal Chemistry Letters, vol. 25, no. 2, 2015, pp. 404-9.
Ivanenkov YA, Vasilevski SV, Beloglazkina EK, et al. Design, synthesis and biological evaluation of novel potent MDM2/p53 small-molecule inhibitors. Bioorg Med Chem Lett. 2015;25(2):404-9.
Ivanenkov, Y. A., Vasilevski, S. V., Beloglazkina, E. K., Kukushkin, M. E., Machulkin, A. E., Veselov, M. S., Chufarova, N. V., Chernyaginab, E. S., Vanzcool, A. S., Zyk, N. V., Skvortsov, D. A., Khutornenko, A. A., Rusanov, A. L., Tonevitsky, A. G., Dontsova, O. A., & Majouga, A. G. (2015). Design, synthesis and biological evaluation of novel potent MDM2/p53 small-molecule inhibitors. Bioorganic & Medicinal Chemistry Letters, 25(2), 404-9. https://doi.org/10.1016/j.bmcl.2014.09.070
Ivanenkov YA, et al. Design, Synthesis and Biological Evaluation of Novel Potent MDM2/p53 Small-molecule Inhibitors. Bioorg Med Chem Lett. 2015 Jan 15;25(2):404-9. PubMed PMID: 25479770.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design, synthesis and biological evaluation of novel potent MDM2/p53 small-molecule inhibitors. AU - Ivanenkov,Yan A, AU - Vasilevski,Sergei V, AU - Beloglazkina,Elena K, AU - Kukushkin,Maksim E, AU - Machulkin,Alexey E, AU - Veselov,Mark S, AU - Chufarova,Nina V, AU - Chernyaginab,Elizaveta S, AU - Vanzcool,Anton S, AU - Zyk,Nikolay V, AU - Skvortsov,Dmitry A, AU - Khutornenko,Anastasia A, AU - Rusanov,Alexander L, AU - Tonevitsky,Alexander G, AU - Dontsova,Olga A, AU - Majouga,Alexander G, Y1 - 2014/10/02/ PY - 2014/04/26/received PY - 2014/09/15/revised PY - 2014/09/24/accepted PY - 2014/12/7/entrez PY - 2014/12/7/pubmed PY - 2015/9/22/medline KW - 3D molecular docking KW - Cell-based assay KW - Dispiro-indolinones KW - MDM2/p53 KW - PPI inhibitors SP - 404 EP - 9 JF - Bioorganic & medicinal chemistry letters JO - Bioorg Med Chem Lett VL - 25 IS - 2 N2 - 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. SN - 1464-3405 UR - https://www.unboundmedicine.com/medline/citation/25479770/Design_synthesis_and_biological_evaluation_of_novel_potent_MDM2/p53_small_molecule_inhibitors_ DB - PRIME DP - Unbound Medicine ER -