Microwave-assisted synthesis, antiproliferative, antibacterial activities, in silico, computational studies and molecular dynamics simulation of new bis- (aryl-based chalcone) derivatives

A new series of bis-(aryl-based chalcone) derivatives 9?15 derived from 4,4?-(ethane-1,2-diylbis(oxy))-bisbenzaldehyde (8) were synthesized, via Claisen?Schmidt condensation, under microwave irradiation (MWI). The newly synthesized bis-chalcones were characterized on the basis of their chemical properties and spectroscopic data. All the synthesized analogues were evaluated for their in vitro antiproliferative activity against breast adenocarcinoma of the CAL51 cell line by MTT assay. Compounds 9 and 10 exhibited the highest cytotoxic activity, with inhibitions of 78.2 % and 74.4 %, respectively, at a concentration of 10 ?M. Furthermore, compounds 9?15 were evaluated for their antibacterial activity. The docking of compounds 9 and 10 with the protein kinase TTK (PDB: 7CHN, 7CIL) related to the triple negative breast cancer (TNBC) was studied to predict their possible binding modes with the kinase. The docking results were agreed with the protein kinase TKK inhibitory studies. Furthermore, the computational analysis was carried out to investigate the molecular structures of the new molecules. These results suggest that analogues 9 and 10 could be promising lead compounds for the continued development of novel antiproliferative agents. The molecular dynamics simulation with computational studies has been performed.