Theoretical investigation of norfloxacin hybrid compounds with silver, copper, and gold metals as potential anticancer agents

Abstract

The strategy of drug repurposing and repositioning in developing hybrid molecules is significant in drug discovery. Norfloxacin (Nor) hybrids, part of the fluoroquinolone class of antibiotics, have demonstrated anticancer properties. Various norfloxacin metal complexes have been synthesized and evaluated for their anticancer potential through docking simulations using AutoDock Vina. To preliminarily identify potential molecular targets for these anticancer compounds, docking studies were conducted with a variety of enzymes and receptor proteins associated with the cell cycle, cell growth, and DNA replication. These targets included cyclin dependent protein kinase-2 (CDK-2), CDK-6, DNA topoisomerases I and II, B cell lymphoma-2 (Bcl-2), and vascular endothelial growth factor receptor-2 (VEGFR-2). Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations were conducted utilizing the B3LYP functional with the 6-311G++ and LanL2DZ basis sets. This study investigated the optimized geometries, molecular electrostatic potential (MEP) maps, key molecular properties, and HOMO-LUMO energy gaps of Nor, Nor zwitterionic structure, and its synthesized compounds ([Ag₂(Nor)₂](NO₃)₂, [Cu(Nor)₂(H2O)₂]SO₄.5H₂O, and [Au(Nor)₂(H₂O)₂]Cl₃).

KEY WORDS: Norfloxacin, Anticancer agents, DFT/ TD-DFT, Molecular docking

Bull. Chem. Soc. Ethiop. 2024, 38(6), 1775-1790.                                                     

DOI: https://dx.doi.org/10.4314/bcse.v38i6.21