Background: Chronic myeloid leukemia (CML) is a blood cancer driven by the BCR-ABL1 fusion protein, where current therapies face challenges like resistance and side effects. Olive leaves contain phenolic compounds, which have shown anti-cancer potential. The aim of the study: To use molecular docking analysis to compare the molecular interactions of selected phenolic compounds in olive leaf extract and Imatinib with the active sites of the Breakpoint Cluster Region (BCR)-Abelson (ABL) fusion protein to identify safer and cost-effective therapeutic candidates for Chronic Myeloid Leukemia (CML). Materials and methods: In this work, we assessed the biological activity of the test substances in silico using the PASS online server. ADME analysis was performed utilizing the SwissADME free online web server, and a toxicology study was done using the AdmetSAR online server. For the in silico molecular docking investigation, the protein structure of the BCR-ABL fusion protein was obtained from the Protein Data Bank (PDB) website, while the ligand structures were obtained from the PubChem website. The binding energy (kcal/mol) was determined using the Autodock Vina software. The protein-ligand interactions were examined using the Discovery Studio Visualizer. Results: In silico molecular docking experiments show that verbascoside, uvaol, loganic acid, secologanin, and cinnamic acid have a high binding affinity to the BCR-ABL protein, with binding energies of -9.2, -9.7, -8.7, -7.3, and -7.4, respectively, which are very close to the binding affinity of the standard medication Imatinib, which has a binding energy of -10.3 Kcal/mol. ADMET analysis and PASS prediction validate the following compounds drug-like properties, i.e., anti-carcinogenic, anti-neoplastic, and anti-neoplastic, along with maintaining Lipinski’s rule of five. Conclusion: The binding affinity of some test compounds compared to Imatinib, as well as their interactions with amino acid residues at the active sites of the BCR-ABL fusion protein, suggest that verbascoside, uvaol, loganic acid, secologanin, and cinnamic acid may bind selectively to CML cells, inhibiting their proliferation and acting as a novel anti-CML agent
Background: Chronic myeloid leukemia (CML) is a blood cancer driven by the BCR-ABL1 fusion protein, where current therapies face challenges like resistance and side effects. Olive leaves contain phenolic compounds, which have shown anti-cancer potential. The aim of the study: To use molecular docking analysis to compare the molecular interactions of selected phenolic compounds in olive leaf extract and Imatinib with the active sites of the Breakpoint Cluster Region (BCR)-Abelson (ABL) fusion protein to identify safer and cost-effective therapeutic candidates for Chronic Myeloid Leukemia (CML). Materials and methods: In this work, we assessed the biological activity of the test substances in silico using the PASS online server. ADME analysis was performed utilizing the SwissADME free online web server, and a toxicology study was done using the AdmetSAR online server. For the in silico molecular docking investigation, the protein structure of the BCR-ABL fusion protein was obtained from the Protein Data Bank (PDB) website, while the ligand structures were obtained from the PubChem website. The binding energy (kcal/mol) was determined using the Autodock Vina software. The protein-ligand interactions were examined using the Discovery Studio Visualizer. Results: In silico molecular docking experiments show that verbascoside, uvaol, loganic acid, secologanin, and cinnamic acid have a high binding affinity to the BCR-ABL protein, with binding energies of -9.2, -9.7, -8.7, -7.3, and -7.4, respectively, which are very close to the binding affinity of the standard medication Imatinib, which has a binding energy of -10.3 Kcal/mol. ADMET analysis and PASS prediction validate the following compounds drug-like properties, i.e., anti-carcinogenic, anti-neoplastic, and anti-neoplastic, along with maintaining Lipinski’s rule of five. Conclusion: The binding affinity of some test compounds compared to Imatinib, as well as their interactions with amino acid residues at the active sites of the BCR-ABL fusion protein, suggest that verbascoside, uvaol, loganic acid, secologanin, and cinnamic acid may bind selectively to CML cells, inhibiting their proliferation and acting as a novel anti-CML agent