Nitroaromatic Antibiotics As Nitrogen Oxide Sources

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2021 Mar 6

PMID 33673069

Citations 12

Authors

Allison M Rice

Yueming Long

S Bruce King

Affiliations

Soon will be listed here.

Abstract

Nitroaromatic antibiotics show activity against anaerobic bacteria and parasites, finding use in the treatment of infections, tuberculosis, trichomoniasis, human African trypanosomiasis, Chagas disease and leishmaniasis. Despite this activity and a clear need for the development of new treatments for these conditions, the associated toxicity and lack of clear mechanisms of action have limited their therapeutic development. Nitroaromatic antibiotics require reductive bioactivation for activity and this reductive metabolism can convert the nitro group to nitric oxide (NO) or a related reactive nitrogen species (RNS). As nitric oxide plays important roles in the defensive immune response to bacterial infection through both signaling and redox-mediated pathways, defining controlled NO generation pathways from these antibiotics would allow the design of new therapeutics. This review focuses on the release of nitrogen oxide species from various nitroaromatic antibiotics to portend the increased ability for these compounds to positively impact infectious disease treatment.

Citing Articles

Novel Prodrug Strategies for the Treatment of Tuberculosis.

Kim C, Jose J, Hay M, Choi P Chem Asian J. 2024; 19(23):e202400944.

PMID: 39179514 PMC: 11613820. DOI: 10.1002/asia.202400944.

In Vitro Activities of Oxazolidinone Antibiotics Alone and in Combination with C-TEMPO against Methicillin-Resistant Biofilms.

Ndukwe A, Qin J, Wiedbrauk S, Boase N, Fairfull-Smith K, Totsika M Antibiotics (Basel). 2023; 12(12).

PMID: 38136740 PMC: 10741017. DOI: 10.3390/antibiotics12121706.

Increased Range of Catalytic Activities of Immobilized Compared to Colloidal Gold Nanoparticles.

Boukoufi C, Boudier A, Clarot I Molecules. 2023; 28(22).

PMID: 38005280 PMC: 10673133. DOI: 10.3390/molecules28227558.

Recent advances in targeted antibacterial therapy basing on nanomaterials.

Geng Z, Cao Z, Liu J Exploration (Beijing). 2023; 3(1):20210117.

PMID: 37323620 PMC: 10191045. DOI: 10.1002/EXP.20210117.

Dual Action of Eeyarestatin 24 on Sec-Dependent Protein Secretion and Bacterial DNA.

Schafer A, Steenhuis M, Jim K, Neef J, OKeefe S, Whitehead R ACS Infect Dis. 2023; 9(2):253-269.

PMID: 36637435 PMC: 9926488. DOI: 10.1021/acsinfecdis.2c00404.

References

Upadhyay A, Chandrakar P, Gupta S, Parmar N, Singh S, Rashid M . Synthesis, Biological Evaluation, Structure-Activity Relationship, and Mechanism of Action Studies of Quinoline-Metronidazole Derivatives Against Experimental Visceral Leishmaniasis. J Med Chem. 2019; 62(11):5655-5671. DOI: 10.1021/acs.jmedchem.9b00628. View

Lopez B, Wink D, Fukuto J . The inhibition of glyceraldehyde-3-phosphate dehydrogenase by nitroxyl (HNO). Arch Biochem Biophys. 2007; 465(2):430-6. DOI: 10.1016/j.abb.2007.06.017. View

Buchieri M, Cimino M, Rebollo-Ramirez S, Beauvineau C, Cascioferro A, Favre-Rochex S . Nitazoxanide Analogs Require Nitroreduction for Antimicrobial Activity in Mycobacterium smegmatis. J Med Chem. 2017; 60(17):7425-7433. DOI: 10.1021/acs.jmedchem.7b00726. View

Church D, Rabin H, Laishley E . Reduction of 2-, 4- and 5-nitroimidazole drugs by hydrogenase 1 in Clostridium pasteurianum. J Antimicrob Chemother. 1990; 25(1):15-23. DOI: 10.1093/jac/25.1.15. View

Kratz J, Bournissen F, Forsyth C, Sosa-Estani S . Clinical and pharmacological profile of benznidazole for treatment of Chagas disease. Expert Rev Clin Pharmacol. 2018; 11(10):943-957. DOI: 10.1080/17512433.2018.1509704. View

Thompson A, OConnor P, Marshall A, Blaser A, Yardley V, Maes L . Development of (6 R)-2-Nitro-6-[4-(trifluoromethoxy)phenoxy]-6,7-dihydro-5 H-imidazo[2,1- b][1,3]oxazine (DNDI-8219): A New Lead for Visceral Leishmaniasis. J Med Chem. 2018; 61(6):2329-2352. PMC: 5867678. DOI: 10.1021/acs.jmedchem.7b01581. View

Hall J, Rouillard K, Suchyta D, Brown M, Ahonen M, Schoenfisc M . Mode of nitric oxide delivery affects antibacterial action. ACS Biomater Sci Eng. 2020; 6(1):433-441. PMC: 7363046. DOI: 10.1021/acsbiomaterials.9b01384. View

Rao D, Mason R . Generation of nitro radical anions of some 5-nitrofurans, 2- and 5-nitroimidazoles by norepinephrine, dopamine, and serotonin. A possible mechanism for neurotoxicity caused by nitroheterocyclic drugs. J Biol Chem. 1987; 262(24):11731-6. View

BEAMAN A, TAUTZ W, Gabriel T, DUSCHINSKY R . THE SYNTHESIS OF AZOMYCIN. J Am Chem Soc. 1965; 87:389-90. DOI: 10.1021/ja01080a048. View

10.

Buisson A, Chevaux J, Bommelaer G, Peyrin-Biroulet L . Diagnosis, prevention and treatment of postoperative Crohn's disease recurrence. Dig Liver Dis. 2012; 44(6):453-60. DOI: 10.1016/j.dld.2011.12.018. View

11.

Searle P, Chen M, Hu L, Race P, Lovering A, Grove J . Nitroreductase: a prodrug-activating enzyme for cancer gene therapy. Clin Exp Pharmacol Physiol. 2004; 31(11):811-6. DOI: 10.1111/j.1440-1681.2004.04085.x. View

12.

Lakshminarayana S, Boshoff H, Cherian J, Ravindran S, Goh A, Jiricek J . Pharmacokinetics-pharmacodynamics analysis of bicyclic 4-nitroimidazole analogs in a murine model of tuberculosis. PLoS One. 2014; 9(8):e105222. PMC: 4139342. DOI: 10.1371/journal.pone.0105222. View

13.

Roldan M, Perez-Reinado E, Castillo F, Moreno-Vivian C . Reduction of polynitroaromatic compounds: the bacterial nitroreductases. FEMS Microbiol Rev. 2008; 32(3):474-500. DOI: 10.1111/j.1574-6976.2008.00107.x. View

14.

DeMaster E, Redfern B, Nagasawa H . Mechanisms of inhibition of aldehyde dehydrogenase by nitroxyl, the active metabolite of the alcohol deterrent agent cyanamide. Biochem Pharmacol. 1998; 55(12):2007-15. DOI: 10.1016/s0006-2952(98)00080-x. View

15.

Cole S, Riccardi G . New tuberculosis drugs on the horizon. Curr Opin Microbiol. 2011; 14(5):570-6. DOI: 10.1016/j.mib.2011.07.022. View

16.

Thompson A, OConnor P, Blaser A, Yardley V, Maes L, Gupta S . Repositioning Antitubercular 6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazoles for Neglected Tropical Diseases: Structure-Activity Studies on a Preclinical Candidate for Visceral Leishmaniasis. J Med Chem. 2016; 59(6):2530-50. DOI: 10.1021/acs.jmedchem.5b01699. View

17.

Voak A, Gobalakrishnapillai V, Seifert K, Balczo E, Hu L, Hall B . An essential type I nitroreductase from Leishmania major can be used to activate leishmanicidal prodrugs. J Biol Chem. 2013; 288(40):28466-76. PMC: 3789948. DOI: 10.1074/jbc.M113.494781. View

18.

Ferreira L, Parra G, Codognato D, Amado A, da Silva R . Light induced cytotoxicity of nitrofurantoin toward murine melanoma. Photochem Photobiol Sci. 2017; 16(7):1071-1078. DOI: 10.1039/c6pp00306k. View

19.

Thompson A, Bonnet M, Lee H, Franzblau S, Wan B, Wong G . Antitubercular Nitroimidazoles Revisited: Synthesis and Activity of the Authentic 3-Nitro Isomer of Pretomanid. ACS Med Chem Lett. 2017; 8(12):1275-1280. PMC: 5733301. DOI: 10.1021/acsmedchemlett.7b00356. View

20.

Anderson R, Shinde S, Maroz A, Boyd M, Palmer B, Denny W . Intermediates in the reduction of the antituberculosis drug PA-824, (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine, in aqueous solution. Org Biomol Chem. 2008; 6(11):1973-80. DOI: 10.1039/b801859f. View