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Ubiquitous Nature of Fluoroquinolones: The Oscillation between Antibacterial and Anticancer Activities

Fluoroquinolones are synthetic antibacterial agents that stabilize the ternary complex of prokaryotic topoisomerase II enzymes (gyrase and Topo IV), leading to extensive DNA fragmentation and bacteria death. Despite the similar structural folds within the critical regions of prokaryotic and eukaryot...

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Autores principales: Idowu, Temilolu, Schweizer, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745469/
https://www.ncbi.nlm.nih.gov/pubmed/29112154
http://dx.doi.org/10.3390/antibiotics6040026
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author Idowu, Temilolu
Schweizer, Frank
author_facet Idowu, Temilolu
Schweizer, Frank
author_sort Idowu, Temilolu
collection PubMed
description Fluoroquinolones are synthetic antibacterial agents that stabilize the ternary complex of prokaryotic topoisomerase II enzymes (gyrase and Topo IV), leading to extensive DNA fragmentation and bacteria death. Despite the similar structural folds within the critical regions of prokaryotic and eukaryotic topoisomerases, clinically relevant fluoroquinolones display a remarkable selectivity for prokaryotic topoisomerase II, with excellent safety records in humans. Typical agents that target human topoisomerases (such as etoposide, doxorubicin and mitoxantrone) are associated with significant toxicities and secondary malignancies, whereas clinically relevant fluoroquinolones are not known to exhibit such propensities. Although many fluoroquinolones have been shown to display topoisomerase-independent antiproliferative effects against various human cancer cells, those that are significantly active against eukaryotic topoisomerase show the same DNA damaging properties as other topoisomerase poisons. Empirical models also show that fluoroquinolones mediate some unique immunomodulatory activities of suppressing pro-inflammatory cytokines and super-inducing interleukin-2. This article reviews the extended roles of fluoroquinolones and their prospects as lead for the unmet needs of “small and safe” multimodal-targeting drug scaffolds.
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spelling pubmed-57454692018-01-02 Ubiquitous Nature of Fluoroquinolones: The Oscillation between Antibacterial and Anticancer Activities Idowu, Temilolu Schweizer, Frank Antibiotics (Basel) Review Fluoroquinolones are synthetic antibacterial agents that stabilize the ternary complex of prokaryotic topoisomerase II enzymes (gyrase and Topo IV), leading to extensive DNA fragmentation and bacteria death. Despite the similar structural folds within the critical regions of prokaryotic and eukaryotic topoisomerases, clinically relevant fluoroquinolones display a remarkable selectivity for prokaryotic topoisomerase II, with excellent safety records in humans. Typical agents that target human topoisomerases (such as etoposide, doxorubicin and mitoxantrone) are associated with significant toxicities and secondary malignancies, whereas clinically relevant fluoroquinolones are not known to exhibit such propensities. Although many fluoroquinolones have been shown to display topoisomerase-independent antiproliferative effects against various human cancer cells, those that are significantly active against eukaryotic topoisomerase show the same DNA damaging properties as other topoisomerase poisons. Empirical models also show that fluoroquinolones mediate some unique immunomodulatory activities of suppressing pro-inflammatory cytokines and super-inducing interleukin-2. This article reviews the extended roles of fluoroquinolones and their prospects as lead for the unmet needs of “small and safe” multimodal-targeting drug scaffolds. MDPI 2017-11-07 /pmc/articles/PMC5745469/ /pubmed/29112154 http://dx.doi.org/10.3390/antibiotics6040026 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Idowu, Temilolu
Schweizer, Frank
Ubiquitous Nature of Fluoroquinolones: The Oscillation between Antibacterial and Anticancer Activities
title Ubiquitous Nature of Fluoroquinolones: The Oscillation between Antibacterial and Anticancer Activities
title_full Ubiquitous Nature of Fluoroquinolones: The Oscillation between Antibacterial and Anticancer Activities
title_fullStr Ubiquitous Nature of Fluoroquinolones: The Oscillation between Antibacterial and Anticancer Activities
title_full_unstemmed Ubiquitous Nature of Fluoroquinolones: The Oscillation between Antibacterial and Anticancer Activities
title_short Ubiquitous Nature of Fluoroquinolones: The Oscillation between Antibacterial and Anticancer Activities
title_sort ubiquitous nature of fluoroquinolones: the oscillation between antibacterial and anticancer activities
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745469/
https://www.ncbi.nlm.nih.gov/pubmed/29112154
http://dx.doi.org/10.3390/antibiotics6040026
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