Design, synthesis, and molecular docking of novel miscellaneous chalcones as p38α mitogen‐activated protein kinase inhibitors

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 GI50 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.