Synthesis and molecular docking study of new benzofuran and furo[3,2-g]chromone-based cytotoxic agents against breast cancer and p38α MAP kinase inhibitors

[Display omitted] •A new set of benzofuran and 5H-furo[3,2-g]chromone linked various heterocyclic functionalities was synthesized.•In vitro cytotoxic evaluation was carried out against MCF-7 cancer cell lines.•In vitro evaluation of p38α MAP kinase inhibition was performed.•Molecular docking study was performed in the active site of the p38α MAP kinase.•VIa induced apoptosis, cell cycle arrest at G2/M phase as well as activation of caspases-9 and -3. This study deals with synthesis of a new set of benzofuran and 5H-furo[3,2-g]chromone linked various heterocyclic functionalities using concise synthetic approaches aiming to gain new antiproliferative candidates against MCF-7 breast cancer cells of p38α MAP kinase inhibiting activity. The biological data proved the significant sensitivity of breast cancer cell lines MCF-7 towards most of the prepared compounds in comparison with doxorubicin. In addition, compounds IIa,b, Va,b, VIa,b, VIIa,b, VIIIa,b, XIc showed significant in vitro p38α MAPK inhibiting potency comparable to the reference standard SB203580. Cell cycle analysis and apoptosis detection data demonstrated that compound VIa induced G2/M phase arrest and apoptosis in MCF-7 cancer cells, in addition to its activation of the caspases-9 and -3. Gold molecular docking studies rationalized the highly acceptable correlation between the calculated docking scores of fitness and the biological data of p38α MAP kinase inhibition. The newly prepared benzofuran and 5H-furo[3,2-g]chromone derivatives might be considered as new promising nuclei in anti-breast cancer chemotherapeutics for further functionalization, optimization and in-depth biological studies.