Synthesis and Biological Evaluation of S-, O- and Se-Containing Dispirooxindoles
Maksim Kukushkin,
Vladimir Novotortsev,
Vadim Filatov,
Yan Ivanenkov,
Dmitry Skvortsov,
Mark Veselov,
Radik Shafikov,
Anna Moiseeva,
Nikolay Zyk,
Alexander Majouga,
Elena Beloglazkina
Affiliations
Maksim Kukushkin
Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1/3, GSP-1, 119991 Moscow, Russia
Vladimir Novotortsev
Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1/3, GSP-1, 119991 Moscow, Russia
Vadim Filatov
Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1/3, GSP-1, 119991 Moscow, Russia
Yan Ivanenkov
Laboratory of Medicinal Chemistry and Bioinformatic, Moscow Institute of Physics and Technology (MIPT), Institutski Pereulok 9, 141701 Dolgoprudny, Russia
Dmitry Skvortsov
Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1/3, GSP-1, 119991 Moscow, Russia
Mark Veselov
Laboratory of Medicinal Chemistry and Bioinformatic, Moscow Institute of Physics and Technology (MIPT), Institutski Pereulok 9, 141701 Dolgoprudny, Russia
Radik Shafikov
Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1/3, GSP-1, 119991 Moscow, Russia
Anna Moiseeva
Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1/3, GSP-1, 119991 Moscow, Russia
Nikolay Zyk
Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1/3, GSP-1, 119991 Moscow, Russia
Alexander Majouga
Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1/3, GSP-1, 119991 Moscow, Russia
Elena Beloglazkina
Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1/3, GSP-1, 119991 Moscow, Russia
A series of novel S-, O- and Se-containing dispirooxindole derivatives has been synthesized using 1,3-dipolar cycloaddition reaction of azomethine ylide generated from isatines and sarcosine at the double C=C bond of 5-indolidene-2-chalcogen-imidazolones (chalcogen was oxygen, sulfur or selenium). The cytotoxicity of these dispiro derivatives was evaluated in vitro using different tumor cell lines. Several molecules have demonstrated a considerable cytotoxicity against the panel and showed good selectivity towards colorectal carcinoma HCT116 p53+/+ over HCT116 p53−/− cells. In particular, good results have been obtained for LNCaP prostate cell line. The performed in silico study has revealed MDM2/p53 interaction as one of the possible targets for the synthesized molecules. However, in contrast to selectivity revealed during the cell-based evaluation and the results obtained in computational study, no significant p53 activation using a reporter construction in p53wt A549 cell line was observed in a relevant concentration range.
