Evaluation of Unique Multidentate Fluoroquinolones as Potential Anticancer and Antimicrobial Compounds Reinforced by Docking Mechanistic Studies on Topoisomerase II and Glyoxalase I with Dual Antioxidative–Anti-Inflammatory Effects

Potential antineoplastic effects of fluoroquinolones (FQs)—resulting from their ability to target human topoisomerase II—are well established. In this study, 16 novel FQs with lipophilic and multidentate properties were synthesized, characterized and evaluated for their potential antiproliferative, radical-scavenging, anti-inflammatory, and antimicrobial activity. Topoisomerase II and Glyoxalase I docking studies were also carried out. Most of the compounds tested exhibited outstanding antiproliferative activity, with IC₅₀ values < 100 μM against most cancer cell lines, including HCT116, HT29, CACO2, SW480, SW620, PANC-1, A375, A549, HELA, MCF7, and T47D. Among the FQs synthesized, the reduced 7Aa, 7Ab, and 7Ac exhibited the highest activity (with IC₅₀ values < 50 μM) against the HCT116, SW480, PANC1, A375, A549, HELA, MCF7, and T47D cell lines. The reduced series 7A displayed moderate and strong antioxidant and anti-inflammatory activity. Most of the synthesized FQs exhibited satisfactory antimicrobial effects with pronounced antifungal potency. In addition, most of the FQs tested displayed marked Glyoxalase I enzyme-inhibitory effects (IC₅₀ values < 100 μM). The results of the SAR study suggest that the C-7 aniline group, C-8–C-7 ethylene diamine bridge, lipophilic N1-isobutyl substituents, and the free acidic (4-oxo-3-COOH) moiety play major roles in enhancing the diverse biological activity of the functionalized FQ scaffold, mainly the reduced 7A series.