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
Hauptverfasser: Mahmoud, Mohamed A, Mohammed, Anber F, Salem, Ola I A, Almutairi, Tahani Mazyad, Bräse, Stefan, Youssif, Bahaa G M
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Sprache:eng
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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.
ISSN:1475-6366
1475-6374
DOI:10.1080/14756366.2024.2305856