Novel Gatifloxacin3-Carboxamide Derivatives as Anti-Tumor Agents: Synthesis, Enantioseparation, and Molecular Docking

Background:: The drug's affinity to the identified target (protein/enzyme) is a critical characteristic in the development of a novel drug. Fluoroquinolone derivatives with a carboxylic group change have improved antimicrobial and anticancer activity while maintaining antibacterial activity similar to parent drugs. Aim:: The rationale upon which synthesis of the new compounds, evaluation of their anticancer activity with in silico study, and suggestion of their mechanism of action is presented in this paper. Methods:: This part describes the practical procedures used for the synthesis of four new gatifloxacin 3-carboxamide derivative, with their spectral data (UV-vis, IR, and 1H-NMR). The enantiosaparation and docking studies are presented and discussed. Results:: Four gatifloxacin 3-carboxamide derivatives were enantioseparated using a high-performance liquid chromatography approach using two distinct polysaccharide-based chiral stationary phases (CSPs). The baseline enantioseparation of all derivatives evaluated in this study was achieved using both coated and immobilized amylose columns. In silico molecular docking study, revealed that all compounds showed good docking score. Conclusion:: The novel Fluoroquinolone caboxamides derivatives could be repositioned as DNA topoisomerase II inhibitors, allowing them to be employed as anticancer agents, according to our in silico study. Experiments in vitro and in vivo are required to confirm their efficacy.