Synthesis of novel 3,5-disubstituted-2-oxindole derivatives as antitumor agents against human nonsmall cell lung cancer
This study was aimed at investigating the antitumor activity of novel 2-oxindole derivatives against a well-characterized human nonsmall cell lung cancer (NSCLC) cell line. Test compounds produced an antiproliferative activity in the low micromolar/submicromolar range of concentrations and significa...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Published: |
American Chemical Society
2013
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| Online Access: | http://hdl.handle.net/20.500.11937/37931 |
| _version_ | 1848755182348795904 |
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| author | Nesi, G. Sestito, S. Mey, V. Ricciardi, S. Falasca, Marco Danesi, R. Lapucci, A. Breschi, M. Fogli, S. Rapposelli, S. |
| author_facet | Nesi, G. Sestito, S. Mey, V. Ricciardi, S. Falasca, Marco Danesi, R. Lapucci, A. Breschi, M. Fogli, S. Rapposelli, S. |
| author_sort | Nesi, G. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | This study was aimed at investigating the antitumor activity of novel 2-oxindole derivatives against a well-characterized human nonsmall cell lung cancer (NSCLC) cell line. Test compounds produced an antiproliferative activity in the low micromolar/submicromolar range of concentrations and significantly induced typical apoptotic morphology with cell shrinkage, nuclear condensation and fragmentation, and rupture of cells into debris in a relatively low percentage of A549 cells. Cell cycle arrest occurred at the G1/S phase (1a and 2), and Akt phosphorylation was significantly inhibited at Thr308 and Ser473. The most active compound (1a) has an IC50 6-fold lower than the Akt inhibitor, perifosine. These data suggest that the new compounds may be cytostatic and may have maximum clinical effects in NSCLC patients who do not respond to EGFR inhibitors. These findings prompt us to further explore the oxindole structure as leading scaffold to design new molecules with potent antitumor activity against NSCLC. © 2013 American Chemical Society. |
| first_indexed | 2025-11-14T08:52:14Z |
| format | Journal Article |
| id | curtin-20.500.11937-37931 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:52:14Z |
| publishDate | 2013 |
| publisher | American Chemical Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-379312018-03-29T09:06:49Z Synthesis of novel 3,5-disubstituted-2-oxindole derivatives as antitumor agents against human nonsmall cell lung cancer Nesi, G. Sestito, S. Mey, V. Ricciardi, S. Falasca, Marco Danesi, R. Lapucci, A. Breschi, M. Fogli, S. Rapposelli, S. This study was aimed at investigating the antitumor activity of novel 2-oxindole derivatives against a well-characterized human nonsmall cell lung cancer (NSCLC) cell line. Test compounds produced an antiproliferative activity in the low micromolar/submicromolar range of concentrations and significantly induced typical apoptotic morphology with cell shrinkage, nuclear condensation and fragmentation, and rupture of cells into debris in a relatively low percentage of A549 cells. Cell cycle arrest occurred at the G1/S phase (1a and 2), and Akt phosphorylation was significantly inhibited at Thr308 and Ser473. The most active compound (1a) has an IC50 6-fold lower than the Akt inhibitor, perifosine. These data suggest that the new compounds may be cytostatic and may have maximum clinical effects in NSCLC patients who do not respond to EGFR inhibitors. These findings prompt us to further explore the oxindole structure as leading scaffold to design new molecules with potent antitumor activity against NSCLC. © 2013 American Chemical Society. 2013 Journal Article http://hdl.handle.net/20.500.11937/37931 10.1021/ml400162g American Chemical Society restricted |
| spellingShingle | Nesi, G. Sestito, S. Mey, V. Ricciardi, S. Falasca, Marco Danesi, R. Lapucci, A. Breschi, M. Fogli, S. Rapposelli, S. Synthesis of novel 3,5-disubstituted-2-oxindole derivatives as antitumor agents against human nonsmall cell lung cancer |
| title | Synthesis of novel 3,5-disubstituted-2-oxindole derivatives as antitumor agents against human nonsmall cell lung cancer |
| title_full | Synthesis of novel 3,5-disubstituted-2-oxindole derivatives as antitumor agents against human nonsmall cell lung cancer |
| title_fullStr | Synthesis of novel 3,5-disubstituted-2-oxindole derivatives as antitumor agents against human nonsmall cell lung cancer |
| title_full_unstemmed | Synthesis of novel 3,5-disubstituted-2-oxindole derivatives as antitumor agents against human nonsmall cell lung cancer |
| title_short | Synthesis of novel 3,5-disubstituted-2-oxindole derivatives as antitumor agents against human nonsmall cell lung cancer |
| title_sort | synthesis of novel 3,5-disubstituted-2-oxindole derivatives as antitumor agents against human nonsmall cell lung cancer |
| url | http://hdl.handle.net/20.500.11937/37931 |