| Title: |
Synthesis and Biological Evaluation of S-, O- and Se-Containing Dispirooxindoles |
| Authors: |
Maksim Kukushkin; Vladimir Novotortsev; Vadim Filatov; Yan Ivanenkov; Dmitry Skvortsov; Mark Veselov; Radik Shafikov; Anna Moiseeva; Nikolay Zyk; Alexander Majouga; Elena Beloglazkina |
| Source: |
Molecules, Vol 26, Iss 7645, p 7645 (2021) |
| Publisher Information: |
MDPI AG |
| Publication Year: |
2021 |
| Collection: |
Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: |
dispirooxindoles; anticancer activity; cytotoxicity; 3D molecular docking; p53/MDM2 interaction; Organic chemistry; QD241-441 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://www.mdpi.com/1420-3049/26/24/7645; https://doaj.org/toc/1420-3049; https://doaj.org/article/12fb39d7fbf749a3bf94a2562909ca7d |
| DOI: |
10.3390/molecules26247645 |
| Availability: |
https://doi.org/10.3390/molecules26247645; https://doaj.org/article/12fb39d7fbf749a3bf94a2562909ca7d |
| Accession Number: |
edsbas.533A709F |
| Database: |
BASE |