Synthesis and biological activity of some vinyl-substituted 2-nitroimidazoles

Abstract

In previous studies 1-methyl-2-nitro-1H-imidazole-5-carboxaldehyde and 1-methyl-2-nitro-5-vinyl-1H-imidazole were found to posses interesting antimicrobial activities. We have now prepared some 2-nitro-1H-imidazoles in which the 5-vinyl chain bears selected functional groups (CHO, COCH3, NO2) as well as nitrogen-condensation derivatives of the carbonyl functions. Furthermore, 5-methyl-2-nitro-1-vinyl-1H-imidazole has been synthesized. All the compounds, and some intermediates, have been assayed for antimicrobial activity. Several of them exhibited significant antibacterial and antitrichomonal activity in mice.

Nitroimidazoles for the Treatment of TB: Past, Present and Future

“…The most active compound in the initial series ( (26) , minimum inhibitory concentration [MIC] = 29.93 µM) had an ethyl at N1 and an unsubstituted vinyl at the 5-position [15]. Subsequently, further vinyl-substituted 2-nitroimidazoles were made with only marginal improvement in antimycobacterial activity (e.g., 1-methyl-2-nitro-5-(2-nitro-hex-1-enyl)-1H-imidazole (31) ) [27]. Further probing of the substitution at the 5-position with larger substituents yielded a marginal improvement in anti-tubercular activity with the most active compound being n -decyl-substituted oxime at the vinylic position (33) [28,29].…”

“…It is notable that 2-amino imidazoles [16], which are thought to be the end-product of intracellular nitroimidazole bioreduction, were also investigated for antimicrobial activity with similar substitutions at the 5-position yielding compounds with moderate anti-tubercular as well as generalized antimicrobial activity. In general, increase in the lipophilicity at the 5-position of the 2-nitroimidazoles increased the antimicrobial activity of Gram-positive bacteria, including Mtb (Figure 2) [27]. …”

Bactericidal activity of 2-nitroimidazole against the active replicating stage of Mycobacterium bovis BCG and Mycobacterium tuberculosis with intracellular efficacy in THP-1 macrophages

“…Based on the superior biological activity of 5-nitroimidazoles, other nitroimidazoles were evaluated initially when this drug class was being considered for its antituberculous potential. Although some reports described the antibacterial activity of a few 2-nitroimidazole derivatives in the 1970s, their antituberculous activity was not appreciated or evaluated further [18,19]. Meanwhile, major attention was created by 5-nitroimidazole derivatives and at least one of them went on to clinical trials [20].…”

Synthetic Nitroimidazoles: Biological Activities and Mutagenicity Relationships

“…Activity was the highest against M. tb when the N-1 substituent was ethyl and the 5-vinyl group was left unsubstituted. These vinyl substituted 2-nitroimidazoles were explored further in a subsequent report by the same group [58] and the best activity against this strain (2 μg/ml) was for 1-methyl-2-nitro-5-(2-nitrohex-1-enyl)-1H-imidazole, a compound with a vinyl group substituted with both an n-butyl group and a second nitro group. Several series of 2-nitro and 2-aminoimidazoles with hydrophilic substitutions at the 5-positions such as oximes and hydrazones were synthesized and tested for antibacterial activity [59][60][61].…”