Design, synthesis, and apoptotic antiproliferative action of new 1,2,3-triazole/1,2,4-oxadiazole hybrids as dual EGFR/VEGFR-2 inhibitors
A novel series of 1,2,3-triazole/1,2,4-oxadiazole hybrids ( - ) was developed as dual inhibitors of EGFR/VEGFR-2. Compounds - were evaluated as antiproliferative agents with Erlotinib as the reference drug. Results demonstrated that most of the tested compounds showed significant antiproliferative a...
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Veröffentlicht in: | Journal of enzyme inhibition and medicinal chemistry 2024-12, Vol.39 (1), p.2305856-2305856 |
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Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
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Zusammenfassung: | A novel series of 1,2,3-triazole/1,2,4-oxadiazole hybrids (
-
) was developed as dual inhibitors of EGFR/VEGFR-2. Compounds
-
were evaluated as antiproliferative agents with Erlotinib as the reference drug. Results demonstrated that most of the tested compounds showed significant antiproliferative action with GI
values ranging from 28 to 104 nM, compared to Erlotinib (GI
= 33 nM), and compounds
-
were the most potent. Compounds
,
,
,
, and
were evaluated as dual EGFR/VEGFR-2 inhibitors. These
experiments demonstrated that compounds
,
, and
are potent antiproliferative agents that may operate as dual EGFR/VEGFR-2 inhibitors. Compounds
,
, and
were evaluated for their apoptotic potential activity, where findings indicated that compounds
,
and
promote apoptosis by activating caspase-3, 8, and Bax and down-regulating the anti-apoptotic Bcl-2. Molecular docking simulations show the binding mode of the most active antiproliferative compounds within EGFR and VEGFR-2 active sites. |
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ISSN: | 1475-6366 1475-6374 |
DOI: | 10.1080/14756366.2024.2305856 |