article · Frontiers in Chemistry
Novel hybrid compounds combining 1,2,4-oxadiazole and quinazoline-4-one structures were evaluated for antiproliferative properties. Testing identified several highly potent candidates, specifically compounds 9b, 9c, 9h, 9k, and 9l. Further in vitro investigations revealed that compounds 9b, 9c, and 9h act as effective dual inhibitors targeting EGFR and BRAFV600E. These three molecules also demonstrated considerable inhibitory effects against the mutant EGFR variant T790M. Cellular studies showed that compound 9b induces cell cycle arrest specifically at the G2/M phase transition alongside apoptosis. Molecular docking analyses clarified the binding mechanisms that underpin the biological activity observed in these leading compounds.
Cancer treatments often face resistance to single-target therapies, particularly through mutations such as EGFR T790M. Developing molecules capable of simultaneously inhibiting multiple cancer-promoting pathways, including EGFR and BRAF variants, offers a strategy for more resilient oncology therapeutics. Identifying dual-action compounds that trigger cell cycle arrest and apoptosis provides useful lead structures for addressing treatment-resistant cancers.
This research is at an early laboratory discovery stage. The identified dual-action inhibitors could serve as lead candidates for pharmaceutical companies and drug development programmes aiming to treat cancers with EGFR or BRAFV600E mutations. Substantial preclinical validation, safety testing, and pharmacokinetic optimisation will be necessary before these molecules can advance toward therapeutic development.
AI-generated from the published abstract. Always read the original work before citing.
The results showed that the majority of the tested compounds showed significant antiproliferative action with 9b, 9c, 9h, 9k, and 9l being the most potent. Compounds 9b, 9c, 9h, 9k, and 9l were tested as EGFR and BRAF<sup>V600E</sup> inhibitors. These <i>in vitro</i> tests revealed that compounds 9b, 9c, and 9h are strong antiproliferative agents that may act as dual EGFR/BRAF<sup>V600E</sup> inhibitors. 9b, 9c, and 9h were further investigated for their inhibitory effect on mutant EGFR (EGFR<sup>T790M</sup>), and the results showed that the tested compounds had considerable inhibitory action. Cell cycle study and apoptosis detection demonstrated that compound 9b exhibits cell cycle arrest at the G2/M transition. Molecular docking simulations reveal the binding mechanism of the most active antiproliferative agents.
This page summarises published work. The authoritative version sits with the publisher.
DOI: 10.3389/fchem.2024.1447618
Is something wrong with this record? Report it or request removal.
Discussion
Have you built on this work, tried to replicate it, or seen it applied in practice? Share what you know. Verified researchers and MARATTO™ domain experts can open a discussion, and any member can reply. Contributions are reviewed before they appear.
No discussion yet. Open the first thread.
New to MARATTO™? Create a free account.
