Title:Fluoroquinolone-induced Glycaemic Aberrations: Could Quinolones be
Repurposed to Serve as New Antidiabetic Agents?
Volume: 18
Issue: 1
Author(s): Omobonlale Ayodele, Setshaba Khanye, Mamosheledi Mothibe and Ntethelelo Sibiya*
Affiliation:
- Division of Pharmacology, Faculty of Pharmacy, Rhodes University, Makhanda 6140, South Africa
Keywords:
Quinolones, diabetes mellitus, antidiabetic activity, hyperglycaemia, hypoglycaemia, glycaemic.
Abstract: Nalidixic acid is a synthetic antibiotic discovered in the 1960s during the synthesis of chloroquine,
an effective drug for treating malaria. Nalidixic acid became the backbone for developing
quinolones that are now widely used clinically for the treatment of various bacterial infections. The
mechanism of action of quinolone involves the inhibition of topoisomerase II and topoisomerase IV.
In attempts to improve the potency of fluoroquinolones, modifications were made; these modifications
resulted in the emergence of newer generations of fluoroquinolones. Also, due to these modifications,
several side effects were noted, including blood glucose control aberrations. Among fluoroquinolones
that disrupt glucose homeostasis is gatifloxacin, which is in the third-generation category. Fluoroquinolones
have been demonstrated to induce glycaemic aberrations by enhancing pancreatic cells' insulin
secretion and interaction with antidiabetic agents via inhibition of cytochrome P450 enzymes. Considering
their ability to induce hypoglycaemia, few studies have reported repurposing of quinolones as
antidiabetic agents. Hyperglycaemia has also been reported to often precede hypoglycaemia. Due to
the ability to decrease blood glucose, it is not surprising that some authors have reported novel quinolone
derivates with antidiabetic properties in experimental studies. However, there is still a paucity of
data regarding the effect of quinolones derivatives on glycaemic control. Understanding how fluoroquinolones
lower blood glucose concentration could serve as the basis for developing novel quinolone
derivatives with the sole purpose of lowering blood glucose concentrations. Although there are various
conventional anti-hyperglycaemic agents, due to their associated shortfalls as well as an increase in the
prevalence of diabetes, the discovery and development of new antidiabetics are warranted.
