Design, synthesis, and apoptotic antiproliferative action of new 1,2,3-triazole/1,2,4-oxadiazole hybrids as dual EGFR/VEGFR-2 inhibitors

Abstract

A novel series of 1,2,3-triazole/1,2,4-oxadiazole hybrids (7a–o) was developed as dual inhibitors of EGFR/VEGFR-2. Compounds 7a–o were evaluated as antiproliferative agents with Erlotinib as the reference drug. Results demonstrated that most of the tested compounds showed significant antiproliferative action with GI₅₀ values ranging from 28 to 104 nM, compared to Erlotinib (GI₅₀ = 33 nM), and compounds 7i–m were the most potent. Compounds 7h, 7i, 7j, 7k, and 7l were evaluated as dual EGFR/VEGFR-2 inhibitors. These in vitro experiments demonstrated that compounds 7j, 7k, and 7l are potent antiproliferative agents that may operate as dual EGFR/VEGFR-2 inhibitors. Compounds 7j, 7k, and 7l were evaluated for their apoptotic potential activity, where findings indicated that compounds 7j, 7k, and 7l 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.

Keywords:

• Triazole
• oxadiazole
• EGFR
• VEGFR-2
• apoptosis
• antiproliferative

Disclosure statement

The author reported no potential conflicts of interests.

Acknowledgements

This work was funded by the Researchers Supporting Project Number [RSP2023R273] at King Saud University, Riyadh, Saudi Arabia. The authors also acknowledge support from the KIT-Publication Fund of the Karlsruhe Institute of Technology.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was funded by the Researchers Supporting Project Number [RSP2023R273] at King Saud University, Riyadh, Saudi Arabia. The authors also acknowledge support from the KIT-Publication Fund of the Karlsruhe Institute of Technology.