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
4 affiliations
- 1School of Pharmacy, University of Jordan, Amman 11942, Jordan
- 2Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan
- 3Faculty of Pharmacy, Al-Azhar University-Gaza, Gaza P.O. Box 1277, Palestine
- 4Department of Chemistry, The University of Jordan, Amman 11942, Jordan
Abstract
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.
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BibTeX
@article{mamdooh2026evaluation,
title = {{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}},
author = {Noor Mamdooh and Yusuf Al-Hiari and Violet Kasabri and Rabab AlBashiti and Randa N. Haddadin and Rula M. Darwish and Qosay Al-Balas and Ihab Almasri and Kamal Sweidan},
journal = {Biomolecules},
year = {2026},
month = nov,
doi = {10.3390/biom16111605},
url = {https://www.mdpi.com/2218-273X/16/11/1605},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Noor Mamdooh
AU - Yusuf Al-Hiari
AU - Violet Kasabri
AU - Rabab AlBashiti
AU - Randa N. Haddadin
AU - Rula M. Darwish
AU - Qosay Al-Balas
AU - Ihab Almasri
AU - Kamal Sweidan
PY - 2026
DA - 2026/11/03
JO - Biomolecules
DO - 10.3390/biom16111605
UR - https://www.mdpi.com/2218-273X/16/11/1605
AB - 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.
SN - 2218-273X
ER -