Synthesis, docking, and biological investigations of new coumarin-piperazine hybrids as potential antibacterial and anticancer agents

Structurally diversified coumarin analogs were found to display a remarkable array of affinity with the different molecular targets. 4-hydroxy-7-methylcoumarin was synthesized from m-cresol and mal-onic acid. In basic media, the 4-hydroxy group of coumarin is replaced further by the bromopropoxy group. Several potent piperazine-containing scaffolds are known for their versatility and medicinal sig-nificance. A series of novel piperazines possessing coumarin derivatives were synthesized from these 4-bromopropoxycoumarin derivatives. These analogs were evaluated for their antibacterial and anticancer activity. Compound 3 (MIC: 12.5 mu g/ml, E. coli) and compound 6 (MIC: 12.5 mu g/ml, E. coli, and 25 mu g/ml, S. aureus) showed potent activity against bacterial pathogens. Compound 3 showed excellent antibacterial activity against S. aureus with a MIC of 6.25 mu g/ml. Compound 6 showed marvelous activity against the MCF-7 cell line with IC50 of 0.003451 mu M, which is far better than the reference Doxorubicin. This is also proclaimed by a docking interaction study of these compounds. In a 100-ns MD simulation, slight RMSD variations and a convergent pattern indicate that the compounds 3 and 6 bound protein complexes did not change structurally or conformationally throughout the simulation run. Furthermore, an overall drug -likeness parameter and insilico predicted ADME properties indicated that compounds could be potential leads for the development of drugs. (c) 2022 Elsevier B.V. All rights reserved.