Imidazolium and benzimidazolium-containing compounds: from simple toxic salts to highly bioactive drugs

Abstract

The toxicity of simple imidazolium and benzimidazolium salts started to be more and more investigated in the last few years and was taken in consideration in the context of microorganisms, plants and more evolved organisms' exposure. However, the toxicity of these salts can be exploited in the development of different biological applications by incorporating them in the structure of compounds that specifically target microorganisms and cancer cells. We highlight in this minireview the way researchers became aware of the inherent problem of the stability and bioaccumulation of imidazolium and benzimidazolium salts and how they found inspiration to exploit their toxicity by incorporating them into new highly potent drugs.

Cytotoxic effects of coumarin substituted benzimidazolium salts against human prostate and ovarian cancer cells

“…Although they were mainly used as Nheterocyclic carbene (NHC) precursors, in recent years, their biological activities attracted much attention. 12 In 2015, Elie et al, reported that benzimidazolium salts perform antibacterial effects by the impairment of membrane permeability. 13 In another study, Liu et al, reported that carbazole substituted benzimidazolium salts perform strong cytotoxicity against various cancer cell lines.…”

Microwave‐assisted synthesis of 1‐substituted‐1H‐benzimidazolium salts: Non‐competitive inhibition of human carbonic anhydrase I and II

“…Besides the neutral benzimidazole derivatives, N , N ‐disubstituted benzimidazolium salts were also examined in medicinal applications. Reported studies revealed that these salts perform antimicrobial, anticancer, and anti‐inflammatory activities. However, studies about the enzyme interaction properties of the benzimidazolium salts are very rare.…”

Tetrasubstituted Imidazolium Salts as Potent Antiparasitic Agents against African and American Trypanosomiases

“…Imidazolium ions are valuable heterocyclic scaffolds due to their broad applications, especially in organocatalysis, and in the synthesis of liquid crystals. Recently, the biological activities of imidazolium and benzimidazolium ions has been reviewed, assessing their toxicity and particularly their wide range of uses in medicinal chemistry [ 8 ]. In 2014, Robello et al [ 9 ] reported that simple symmetric imidazolium salts A ( Figure 1 ) with bulky aromatic moieties on the N 1 and N 3 positions are active against T. cruzi .…”

“…The putative biological target of these compounds has been postulated as being linked with the parasite mitochondrion. The major differences between these organelles in parasites and mammals could explain the selective toxicity of the imidazolium salts toward trypanosomes [ 8 , 9 ]. In this respect, we recently reported the potent antitrypanosomal activity of a family of azine-fused aminoimidazolium salts B ( Figure 1 ) arising from a trimethylsilyl-catalyzed interaction of azines with isocyanides in a multicomponent manner [ 10 ].…”