Login Register Cart 0
Generic placeholder image

Current Reviews in Clinical and Experimental Pharmacology

Editor-in-Chief

ISSN (Print): 2772-4328
ISSN (Online): 2772-4336

Back
Journal Home About Journal Editorial Board Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Fluoroquinolone-induced Glycaemic Aberrations: Could Quinolones be Repurposed to Serve as New Antidiabetic Agents?

Author(s): Omobonlale Ayodele, Setshaba Khanye, Mamosheledi Mothibe and Ntethelelo Sibiya*

Volume 18, Issue 1, 2023

Published on: 18 April, 2022

Page: [12 - 21] Pages: 10

DOI: 10.2174/2772432817666220218101050

Price: $65

Open Access Journals Promotions 2
conference banner
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.

Keywords: Quinolones, diabetes mellitus, antidiabetic activity, hyperglycaemia, hypoglycaemia, glycaemic.

« Previous Next »
Graphical Abstract

[1]
Cheng, G.; Hao, H.; Dai, M.; Liu, Z.; Yuan, Z. Antibacterial action of quinolones: From target to network. Eur. J. Med. Chem., 2013, 66, 555-562.
[http://dx.doi.org/10.1016/j.ejmech.2013.01.057] [PMID: 23528390]
[2]
Andriole, V.T. The quinolones: Past, present, and future. Clin. Infect. Dis., 2005, 41(Suppl. 2), S113-S119.
[http://dx.doi.org/10.1086/428051] [PMID: 15942877]
[3]
Naidoo, A.; Naidoo, K.; McIlleron, H.; Essack, S.; Padayatchi, N. A review of moxifloxacin for the treatment of drug-susceptible tuberculosis. J. Clin. Pharmacol., 2017, 57(11), 1369-1386.
[http://dx.doi.org/10.1002/jcph.968] [PMID: 28741299]
[4]
Park-Wyllie, L.Y.; Juurlink, D.N.; Kopp, A.; Shah, B.R.; Stukel, T.A.; Stumpo, C.; Dresser, L.; Low, D.E.; Mamdani, M.M. Outpatient gatifloxacin therapy and dysglycemia in older adults. N. Engl. J. Med., 2006, 354(13), 1352-1361.
[http://dx.doi.org/10.1056/NEJMoa055191] [PMID: 16510739]
[5]
Lesher, G.Y.; Froelich, E.J.; Gruett, M.D.; Bailey, J.H.; Brundage, R.P. 1, 8-Naphthyridine derivatives. A new class of chemotherapeutic agents. J. Med. Pharm. Chem., 1962, 91(5), 1063-1065.
[http://dx.doi.org/10.1021/jm01240a021] [PMID: 14056431]
[6]
Aldred, K.J.; Kerns, R.J.; Osheroff, N. Mechanism of quinolone action and resistance. Biochemistry, 2014, 53(10), 1565-1574.
[http://dx.doi.org/10.1021/bi5000564] [PMID: 24576155]
[7]
Brighty, K.E.; Gootz, T.D. Chemistry and mechanism of action of the quinolone antibacterials. In: The quinolones; , 2000; pp. 33-97.
[http://dx.doi.org/10.1016/B978-012059517-4/50003-9]
[8]
Holmes, B.; Brogden, R.N.; Richards, D.M. Norfloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs, 1985, 30(6), 482-513.
[http://dx.doi.org/10.2165/00003495-198530060-00003] [PMID: 3908074]
[9]
Pham, T.D.M.; Ziora, Z.M.; Blaskovich, M.A.T. Quinolone antibiotics. MedChemComm, 2019, 10(10), 1719-1739.
[http://dx.doi.org/10.1039/C9MD00120D] [PMID: 31803393]
[10]
Wagstaff, A.J.; Balfour, J.A. Grepafloxacin. Drugs, 1997, 53(5), 817-824.
[http://dx.doi.org/10.2165/00003495-199753050-00007] [PMID: 9129868]
[11]
Balfour, J.A.; Wiseman, L.R. Moxifloxacin. Drugs, 1999, 57(3), 363-373.
[http://dx.doi.org/10.2165/00003495-199957030-00007] [PMID: 10193688]
[12]
Saravolatz, L.D.; Leggett, J. Gatifloxacin, gemifloxacin, and moxifloxacin: The role of 3 newer fluoroquinolones. Clin. Infect. Dis., 2003, 37(9), 1210-1215.
[http://dx.doi.org/10.1086/378809] [PMID: 14557966]
[13]
Garey, K.W.; Amsden, G.W. Trovafloxacin: An overview. Pharmacotherapy, 1999, 19(1), 21-34.
[http://dx.doi.org/10.1592/phco.19.1.21.30507] [PMID: 9917076]
[14]
Proks, P.; Reimann, F.; Green, N.; Gribble, F.; Ashcroft, F. Sulfonylurea stimulation of insulin secretion. Diabetes, 2002, 51(Suppl. 3), S368-S376.
[http://dx.doi.org/10.2337/diabetes.51.2007.S368] [PMID: 12475777]
[15]
Viollet, B.; Guigas, B.; Sanz Garcia, N.; Leclerc, J.; Foretz, M.; Andreelli, F. Cellular and molecular mechanisms of metformin: An overview. Clin. Sci. (Lond.), 2012, 122(6), 253-270.
[http://dx.doi.org/10.1042/CS20110386] [PMID: 22117616]
[16]
Lewis, R.J.; Mohr, J.F., III Dysglycaemias and fluoroquinolones. Drug Saf., 2008, 31(4), 283-292.
[http://dx.doi.org/10.2165/00002018-200831040-00002] [PMID: 18366239]
[17]
Telfer, S.J. Fluoroquinolone antibiotics and type 2 diabetes mellitus. Med. Hypotheses, 2014, 83(3), 263-269.
[http://dx.doi.org/10.1016/j.mehy.2014.05.013] [PMID: 24947193]
[18]
Aspinall, S.L.; Good, C.B.; Jiang, R.; McCarren, M.; Dong, D.; Cunningham, F.E. Severe dysglycemia with the fluoroquinolones: A class effect? Clin. Infect. Dis., 2009, 49(3), 402-408.
[http://dx.doi.org/10.1086/600294] [PMID: 19545207]
[19]
El Ghandour, S.; Azar, S.T. Dysglycemia associated with quinolones. Prim. Care Diabetes, 2015, 9(3), 168-171.
[http://dx.doi.org/10.1016/j.pcd.2014.10.006] [PMID: 25466161]
[20]
Liu, H.H. Safety profile of the fluoroquinolones: Focus on levofloxacin. Drug Saf., 2010, 33(5), 353-369.
[http://dx.doi.org/10.2165/11536360-000000000-00000] [PMID: 20397737]
[21]
Sibiya, H.P.; Mabandla, M.V.; Musabayane, C.T. The effects of transdermally delivered oleanolic acid on malaria parasites and blood glucose homeostasis in P. berghei-infected male Sprague-Dawley rats. PLoS One, 2016, 11(12), e0167132.
[http://dx.doi.org/10.1371/journal.pone.0167132] [PMID: 27907019]
[22]
Halaby, M.J.; Kastein, B.K.; Yang, D.Q. Chloroquine stimulates glucose uptake and glycogen synthase in muscle cells through activation of Akt. Biochem. Biophys. Res. Commun., 2013, 435(4), 708-713.
[http://dx.doi.org/10.1016/j.bbrc.2013.05.047] [PMID: 23702482]
[23]
McGill, J.B.; Johnson, M.; Hurst, S.; Cade, W.T.; Yarasheski, K.E.; Ostlund, R.E.; Schechtman, K.B.; Razani, B.; Kastan, M.B.; McClain, D.A.; de Las Fuentes, L.; Davila-Roman, V.G.; Ory, D.S.; Wickline, S.A.; Semenkovich, C.F. Low dose chloroquine decreases insulin resistance in human metabolic syndrome but does not reduce carotid intima-media thickness. Diabetol. Metab. Syndr., 2019, 11(1), 61.
[http://dx.doi.org/10.1186/s13098-019-0456-4] [PMID: 31384309]
[24]
Yabe, K.; Yamamoto, Y.; Suzuki, T.; Takada, S.; Mori, K. Functional and morphological characteristics of pancreatic islet lesions induced by quinolone antimicrobial agent gatifloxacin in rats. Toxicol. Pathol., 2019, 47(1), 35-43.
[http://dx.doi.org/10.1177/0192623318809062] [PMID: 30407147]
[25]
Yamada, C.; Nagashima, K.; Takahashi, A.; Ueno, H.; Kawasaki, Y.; Yamada, Y.; Seino, Y.; Inagaki, N. Gatifloxacin acutely stimulates insulin secretion and chronically suppresses insulin biosynthesis. Eur. J. Pharmacol., 2006, 553(1-3), 67-72.
[http://dx.doi.org/10.1016/j.ejphar.2006.09.043] [PMID: 17070519]
[26]
Tomita, T.; Onishi, M.; Sato, E.; Kimura, Y.; Kihira, K. Gatifloxacin induces augmented insulin release and intracellular insulin depletion of pancreatic islet cells. Biol. Pharm. Bull., 2007, 30(4), 644-647.
[http://dx.doi.org/10.1248/bpb.30.644] [PMID: 17409495]
[27]
Ghaly, H.; Kriete, C.; Sahin, S.; Pflöger, A.; Holzgrabe, U.; Zünkler, B.J.; Rustenbeck, I. The insulinotropic effect of fluoroquinolones. Biochem. Pharmacol., 2009, 77(6), 1040-1052.
[http://dx.doi.org/10.1016/j.bcp.2008.11.019] [PMID: 19073153]
[28]
Maeda, N.; Tamagawa, T.; Niki, I.; Miura, H.; Ozawa, K.; Watanabe, G.; Nonogaki, K.; Uemura, K.; Iguchi, A. Increase in insulin release from rat pancreatic islets by quinolone antibiotics. Br. J. Pharmacol., 1996, 117(2), 372-376.
[http://dx.doi.org/10.1111/j.1476-5381.1996.tb15201.x] [PMID: 8789393]
[29]
Saraya, A.; Yokokura, M.; Gonoi, T.; Seino, S. Effects of fluoroquinolones on insulin secretion and β-cell ATP-sensitive K+ channels. Eur. J. Pharmacol., 2004, 497(1), 111-117.
[http://dx.doi.org/10.1016/j.ejphar.2004.06.032] [PMID: 15321742]
[30]
Owens, R.C., Jr; Ambrose, P.G. Antimicrobial safety: Focus on fluoroquinolones. Clin. Infect. Dis., 2005, 41(Suppl. 2), S144-S157.
[http://dx.doi.org/10.1086/428055] [PMID: 15942881]
[31]
Frothingham, R. Glucose homeostasis abnormalities associated with use of gatifloxacin. Clin. Infect. Dis., 2005, 41(9), 1269-1276.
[http://dx.doi.org/10.1086/496929] [PMID: 16206101]
[32]
Yoshimatsu, Y.; Ishizaka, T.; Chiba, K.; Mori, K. Usefulness of simultaneous and sequential monitoring of glucose level and electrocardiogram in monkeys treated with gatifloxacin under conscious and nonrestricted conditions. Exp. Anim., 2018, 67(2), 281-290.
[http://dx.doi.org/10.1538/expanim.17-0136] [PMID: 29311442]
[33]
Brunton, L.L.; Chabner, B.A.; Knollman, B.C. Goodman & Gilman’s The pharmacological basis of therapeutics, 12th ed.; The McGraw-Hill companies: United State of America, 2011, p. 1240.
[34]
Catero, M. Dysglycemia and fluoroquinolones: Are you putting patients at risk? J. Fam. Pract., 2007, 56(2), 101-107.
[PMID: 17270116]
[35]
Gajjar, D.A.; LaCreta, F.P.; Kollia, G.D.; Stolz, R.R.; Berger, S.; Smith, W.B.; Swingle, M.; Grasela, D.M. Effect of multiple-dose gatifloxacin or ciprofloxacin on glucose homeostasis and insulin production in patients with noninsulin-dependent diabetes mellitus maintained with diet and exercise. Pharmacotherapy, 2000, 20(6 Pt 2), 76S-86S.
[http://dx.doi.org/10.1592/phco.20.8.76s.35182] [PMID: 10850524]
[36]
Grasela, D.M. Clinical pharmacology of gatifloxacin, a new fluoroquinolone. Clin. Infect. Dis., 2000, 31(Suppl. 2), S51-S58.
[http://dx.doi.org/10.1086/314061] [PMID: 10984329]
[37]
Biggs, W.S. Hypoglycemia and hyperglycemia associated with gatifloxacin use in elderly patients. J. Am. Board Fam. Pract., 2003, 16(5), 455-457.
[http://dx.doi.org/10.3122/jabfm.16.5.455] [PMID: 14645336]
[38]
Lodise, T.; Graves, J.; Miller, C.; Mohr, J.F.; Lomaestro, B.; Smith, R.P. Effects of gatifloxacin and levofloxacin on rates of hypoglycemia and hyperglycemia among elderly hospitalized patients. Pharmacotherapy, 2007, 27(11), 1498-1505.
[http://dx.doi.org/10.1592/phco.27.11.1498] [PMID: 17963459]
[39]
Mohr, J.F.; McKinnon, P.S.; Peymann, P.J.; Kenton, I.; Septimus, E.; Okhuysen, P.C. A retrospective, comparative evaluation of dysglycemias in hospitalized patients receiving gatifloxacin, levofloxacin, ciprofloxacin, or ceftriaxone. Pharmacotherapy, 2005, 25(10), 1303-1309.
[http://dx.doi.org/10.1592/phco.2005.25.10.1303] [PMID: 16185173]
[40]
Vinh, H.; Anh, V.T.; Anh, N.D.; Campbell, J.I.; Hoang, N.V.; Nga, T.V.; Nhu, N.T.; Minh, P.V.; Thuy, C.T.; Duy, P.T.; Phuong, T.; Loan, H.T.; Chinh, M.T.; Thao, N.T.; Tham, N.T.; Mong, B.L.; Bay, P.V.; Day, J.N.; Dolecek, C.; Lan, N.P.; Diep, T.S.; Farrar, J.J.; Chau, N.V.; Wolbers, M.; Baker, S. A multi-center randomized trial to assess the efficacy of gatifloxacin versus ciprofloxacin for the treatment of shigellosis in Vietnamese children. PLoS Negl. Trop. Dis., 2011, 5(8), e1264.
[http://dx.doi.org/10.1371/journal.pntd.0001264] [PMID: 21829747]
[41]
Kennedy, K.E.; Teng, C.; Patek, T.M.; Frei, C.R. Hypoglycemia associated with antibiotics alone and in combination with sulfonylureas and meglitinides: An epidemiologic surveillance study of the FDA adverse event reporting system (FAERS). Drug Saf., 2020, 43(4), 363-369.
[PMID: 31863282]
[42]
Berhe, A.; Russom, M.; Bahran, F.; Hagos, G. Ciprofloxacin and risk of hypolycemia in non-diabetic patients. J. Med. Case Reports, 2019, 13(1), 142.
[http://dx.doi.org/10.1186/s13256-019-2083-y] [PMID: 31078137]
[43]
Roberge, R.J.; Kaplan, R.; Frank, R.; Fore, C. Glyburideciprofloxacin interaction with resistant hypoglycemia. Ann. Emerg. Med., 2000, 36(2), 160-163.
[http://dx.doi.org/10.1067/mem.2000.108617] [PMID: 10918110]
[44]
Edmont, D.; Rocher, R.; Plisson, C.; Chenault, J. Synthesis and evaluation of quinoline carboxyguanidines as antidiabetic agents. Bioorg. Med. Chem. Lett., 2000, 10(16), 1831-1834.
[http://dx.doi.org/10.1016/S0960-894X(00)00354-1] [PMID: 10969979]
[45]
Muluk, R.; Kothawade, P.; Kulkarni, G.; Ingale, P. Synthesis and evaluaton of some novel benzimidazole and quinolone derivatives for their antifungal and antidiabetic activity. World J. Pharm. Pharm. Sci., 2017, 7(1), 1263-1278.

Rights & Permissions Print Cite
Article Metrics
65
2
Wayfinder Image
Open Access Journals Promotions
© 2024 Bentham Science Publishers | Privacy Policy