Towards anticancer fluoroquinolones: A review article

Abstract

Different studies about the anticancer potential of several medically used antibacterial fluoroquinolones have been established. Fluoroquinolone derivatives, like some anticancer drugs, such as doxorubicin, can achieve antitumor activity via poisoning of type II human DNA topoisomerases. Interestingly, structural features required for the anticancer activity of quinolones have been determined. Most of the chemical modifications required to convert antibacterially acting fluoroquinolones into their anticancer analogs were at position 7 and the carboxylic group at position 3. This review highlights the antitumor potential of fluoroquinolones in general and summarizes the chemical modifications carried out on fluoroquinolones to become anticancer agents. Moreover, the review gives a quick recap on metal ion chelates with fluoroquinolones and their substantial role in topoisomerase poisoning and antitumor potential improvement. Hence, it should be highly interesting for researchers attempting to design and synthesize novel anticancer fluoroquinolone candidates. K E Y W O R D S anticancer, DNA topoisomerase, metal ion complexes, quinolones Arch Pharm Chem Life Sci. 2019;352:1800376.wileyonlinelibrary.com/journal/ardp

In silico drug repurposing in COVID-19: A network-based analysis

“…This category includes both tyrosine kinase inhibitors (TRK inhibitors) [Entrectinib, Larotrectinib] and drugs inhibiting the activity of human topoisomerase II, such as fluoroquinolones (ofloxacin, ciprofloxacin) [52] , [53] . Due to their ability to act as antiproliferative molecules, these drugs have emerged as promising antitumor repurposed compounds.…”

Modulating microRNA Processing: Enoxacin, the Progenitor of a New Class of Drugs

“…However, vosaroxin is one of the many quinolones that act as topo II inhibitors. 69 It appears evident that the mechanism of action of vosaroxin, like that of other quinolone topo II inhibitors, is very similar to the mechanism adopted by antimicrobial quinolones in inhibiting bacterial DNA gyrase or topoisomerase IV. 74 This similarity in the mechanism of action, especially in the mode of action, makes the building of a differentiated SAR around the quinolone class very difficult.…”

“…In parallel, over the years, ciprofloxacin and other quinolones have often been reported as promising anticancer agents endowed with different mechanisms of action, differing from the modulation of miRNA maturation and human topo II inhibition. 69 In our opinion, most of these compounds could be involved in modulating miRNA maturation because any interference in this process can produce several downstream changes in cellular mechanisms. We know that enoxacin is able to enhance miRNA maturation in cells; however, ignoring this effect, we can state that enoxacin can ( i ) increase p53 expression, ( ii ) improve Dicer activity, ( iii ) reduce HDAC1 and SIRT1 levels, and ( iv ) lower EMT markers, among other effects.…”

The replicative CMG helicase: the ideal target for cancer therapy

“…Because during DNA replication topoisomerases progress in front of helicases and replicative machinery, it is topoisomerase activity that must be the most affected by the present of Ciprofloxacin. Indeed, all cases of Ciprofloxacin-induced cytotoxicity toward cancer cells are attributed to the inhibition of type 2 DNA topoisomerases [71].…”