Background: The affinity of a drug 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: In this paper, the rationale upon which synthesis of the new compounds is based, evaluation of their anticancer activity with in silico study, and suggestion of their mechanism of action are presented.
Methods: Different practical procedures were used for the synthesis of four new gatifloxacin 3- carboxamide derivatives with their spectral data (UV-vis, IR, and 1H-NMR). The enantioseparation 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. However, in vitro and in vivo experiments are required to confirm their efficacy.
Keywords: Gatifloxacin, 3-Carboxamides derivatives, HPLC, chiral separation, docking, quinolones.