Pyrrole-Fused Benzoxazinones/Quinoxalinones: Molecular Dynamic Simulation, Antiproliferative and Antibacterial Activities

摘要

A series of novel pyrrole fused benzoxazinones/quinoxalinones has been evaluated for antiproliferative activity against breast cancer cell line, MCF7 and treatment-resistant triple-negative breast cancer cell line MDA-MB-231. Among which pyrroloqui- noxalinones exhibited higher cytotoxicity. Furthermore, they showed insignificant cellular cytotoxicity in normal human cell HEK293T when treated with their respective IC50 concentra- tions. In silico molecular docking, study suggests that the inhibitory mechanism of pyrroloquinoxalinones probably medi- ated via modulation of breast cancer targets such as VEGFR2 and EGFR. The stability of target protein (VEGFR2 and EGFR)- ligand (pyrroloquinoxalinones) interactions was validated by Molecular dynamic simulation (50 ns). Additionally, pyrroloben- zoxazinones/quinoxalinones were evaluated for in vitro anti- bacterial activity against Gram-positive and Gram-negative bacterial strains. All the compounds exhibited significant antibacterial activity (IC50 0.034-15.4 μM) towards the tested bacterial strains. These findings indicate that pyrrolobenzoxazi- nones/quinoxalinones are valuable scaffolds for the develop- ment of potent anticancer and antibacterial compounds.