1. Design, Synthesis, and Molecular Docking of Novel Miscellaneous Chalcones as p38α Mitogen-Activated Protein Kinase Inhibitors.
- Author
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Zeid MM, El-Badry OM, Elmeligie S, and Hassan RA
- Subjects
- Humans, Molecular Docking Simulation, Cell Cycle Checkpoints, Doxorubicin pharmacology, Protein Kinase Inhibitors chemistry, Apoptosis, Molecular Structure, Cell Proliferation, Structure-Activity Relationship, Cell Line, Tumor, Mitogen-Activated Protein Kinase 14 chemistry, Mitogen-Activated Protein Kinase 14 metabolism, Chalcones pharmacology, Antineoplastic Agents chemistry
- Abstract
New chalcones were synthesized and evaluated to serve as p38-α type of mitogen-activated protein kinase (MAPK) inhibitors. According to the National Cancer Institute, the findings indicated that at a 10 μM dosage, compounds 3a and 6 were the most active among all the compounds examined, with mean growth inhibition% of 94.83 and 58.49, respectively. In 5-dose testing, they showed anticancer activity in the micro-molar range with GI
50 in the range of 1.41-46.1 and 2.07-31.3 μM, respectively. Besides, powerful activity, especially against the leukaemia cell lines and good selectivity to cancer cells compared to normal PCS-800-017 with a selectivity index=12.41 and 23.77, respectively. Compounds 3a and 6 inhibited p38α MAPK with IC50 values of 0.1462±0.0063 and 0.4356±0.0189 μM, correspondingly. 3a showed good inhibition for HL-60(TB) cells and induced cell cycle arrest in HL-60(TB) cells at the G2/M phase. Besides, it elevated the total apoptosis by 14.68-fold and increased the caspase-3 level by 3.52-fold compared with doxorubicin, which raised it by 4.30-fold, inducing apoptosis by acting as caspase-dependent inducers. These results suggest that 3a is a promising antiproliferative and p38α MAPK inhibitor, confirmed by molecular docking with high compatibility 3a with the p38α MAPK binding site., (© 2024 Wiley‐VHCA AG, Zurich, Switzerland.)- Published
- 2024
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