Triazole-Schiff Base Hybrids as Potential Dual Inhibitors of Bcl-2 and EGFR: Synthesis, Characterization, and Computational Insights

Mohamed Enneiymy; Abd Elaziz Rahhou; Younesse Ait Elmachkouri; Ali Hasnaoui; Mohamed Labd Taha; Moulay Youssef Ait Itto; Saad H Alotaibi; Ali Oubella; Reda A Haggam

doi:10.1007/s10895-025-04622-2

Triazole-Schiff Base Hybrids as Potential Dual Inhibitors of Bcl-2 and EGFR: Synthesis, Characterization, and Computational Insights

J Fluoresc. 2025 Dec 6. doi: 10.1007/s10895-025-04622-2. Online ahead of print.

Authors

Mohamed Enneiymy¹, Abd Elaziz Rahhou², Younesse Ait Elmachkouri³, Ali Hasnaoui², Mohamed Labd Taha³, Moulay Youssef Ait Itto⁴, Saad H Alotaibi⁵, Ali Oubella³, Reda A Haggam⁶

Affiliations

¹ Laboratory of Organic & Physical Chemistry, Applied Bioorganic Chemistry Team, Faculty of Sciences, Ibnou Zohr University, Agadir, Morocco. mohamed.enneiymy@gmail.com.
² Laboratory of Molecular Chemistry, Faculty of Sciences Semlalia Marrakech, Cadi Ayyad University, UCA, B.P. 2390, Marrakech, 40000, Morocco.
³ Laboratory of Organic & Physical Chemistry, Applied Bioorganic Chemistry Team, Faculty of Sciences, Ibnou Zohr University, Agadir, Morocco.
⁴ Laboratory of Organic Synthesis and Physico-Molecular Chemistry, Department of Chemistry, Faculty of Sciences Semlalia, Universit´e Cadi Ayyad, BP PO Box 2390, Marrakech, 40001, Morocco.
⁵ Department of Chemistry, Turabah University College, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia.
⁶ Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah, 42351, Saudi Arabia. relhaggan@iu.edu.sa.

PMID: 41351735
DOI: 10.1007/s10895-025-04622-2

Abstract

Cancer remains a major global health challenge, requiring the development of novel therapeutic agents with high efficacy and minimal side effects. In this study, we designed and synthesised a series of hybrid molecules incorporating triazoles, Schiff bases and substituted aromatic motifs, targeting the key oncogenic proteins Bcl-2 and EGFR. The compounds were characterised using spectroscopic techniques and their physicochemical and computational insights were assessed using in silico tools. ADMET showed poor toxicity, Molecular docking studies revealed high binding affinities for both Bcl-2 (docking energies: -6.9 to -7.1 kcal/mol) and EGFR (-9.6 to -10.0 kcal/mol), with compound 5d showing the highest affinity. Molecular dynamics simulations confirmed the stability of the protein-ligand complexes over 200 ns, with RMSD, RMSF, Rg and SASA analyses confirming favourable binding interactions. The compounds showed excellent similarity to drugs, high gastrointestinal absorption and low risk of toxicity. These results suggest that the synthesised hybrids hold great promise as as potential dual-targeted anti-cancer agents warranting further experimental investigation.

Keywords: ADMET prediction; Bcl-2 predicted inhibition; EGFR predicted inhibition; Molecular docking; Molecular dynamics simulation; Potential anticancer agents; Triazole-Schiff base hybrids.