2-Nitro-1-vinyl-1H-imidazole

Afonso Santine M M Velez,Debora Decote-Ricardo,Paulo Pitasse-Santos,Gabriela Alves De Souza,Marco Edilson Freire De Lima,Douglas Chaves De Alcântara Pinto

doi:10.3390/m1326

Afonso Santine M M Velez, Debora Decote-Ricardo + Show 4 more

Open Access

https://doi.org/10.3390/m1326

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Journal: Molbank	Publication Date: Jan 27, 2022
License type: CC BY 4.0

Affiliation: Universidade Federal Rural do Rio de Janeiro

Abstract

Nitroimidazoles are pharmacophoric groups responsible for important antiparasitic activity against several infectious diseases. 2-Nitroimidazoles are found in some antiparasitic drugs and are one of the main moieties responsible for the biological activities exhibited. As an example, we can mention the drug benznidazole, the only drug available in Brazil for the treatment of Chagas disease. This work describes an efficient methodology for the synthesis of 2-nitro-1-vinyl-1H-imidazole through a simple and direct approach, as well as its full characterization and biological assessment. The antiparasitic evaluation of 2-nitro-1-vinyl-1H-imidazole against Trypanosoma cruzi (Tulahuen C2C4-LacZ strain) showed IC50 = 4.8 μM on amastigotes and low cytotoxicity against LLC-MK2 cells (IC50 > 500 μM), validating 2-nitro-1-vinyl-1H-imidazole as a biologically active structural subunit for anti-T. cruzi activity. The results presented herein demonstrate that 2-nitro-1-vinyl-1H-imidazole can be easily obtained, possessing great potential for use in the design of new antichagasic drugs through a molecular hybridization strategy using known coupling reactions.

Highlights

Nitroimidazoles are a class of molecules that present in their structure a five-membered heterocycle, with two nitrogen atoms in the 1 and 3 positions and a nitro group that can appear in the 2, 4 or 5 position
The first nitroimidazole isolated and characterized from a natural source was azomycin 1 (2-nitroimidazole), a natural antibiotic from Streptomyces eurocidicus, in the 1950s, while a group of scientists analyzed the activity of this extract against Trichomonas vaginalis [1,2]. 2-Nitro-1-vinyl-1H-imidazole 2 was first described in the 1984 Hoffman-La Roche patent as an antiparasitic agent with filarcidal activity, exhibiting average ED90 values against Litomosoides sigmodontis, formerly known as L. carinii, in cotton rats at doses of 12 mg/kg [3,4]
The use of nitroimidazoles as antiparasitic agents deserves significant attention, since important drugs currently used to treat both parasitic and bacterial infections have a nitroheterocycle group in their structure, such as benznidazole 3 (2-nitroimidazole) and nifurtimox 4 (5-nitrofuran). These are the only drugs used to treat Chagas disease that possess protozoa hemoflagellate T. cruzi as an etiologic agent [5,6,7], in addition to megazole 5 and fexinidazol 6, which have great antichagasic potential [8], and metronidazole 7 (2-methyl-5-nitroimidazole) for the treatment of infections caused by protozoa such as Trichomonas vaginalis [1], Giardia Lamblia [9] and bacterial infections

Summary

Introduction

Nitroimidazoles are a class of molecules that present in their structure a five-membered heterocycle, with two nitrogen atoms in the 1 and 3 positions and a nitro group that can appear in the 2, 4 or 5 position. The use of nitroimidazoles as antiparasitic agents deserves significant attention, since important drugs currently used to treat both parasitic and bacterial infections have a nitroheterocycle group in their structure, such as benznidazole 3 (2-nitroimidazole) and nifurtimox 4 (5-nitrofuran) These are the only drugs used to treat Chagas disease that possess protozoa hemoflagellate T. cruzi as an etiologic agent [5,6,7], in addition to megazole 5 and fexinidazol 6 (both 1-methyl-5-nitroimidazole), which have great antichagasic potential [8], and metronidazole 7 (2-methyl-5-nitroimidazole) for the treatment of infections caused by protozoa such as Trichomonas vaginalis [1], Giardia Lamblia [9] and bacterial infections.

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Conclusion