Benzimidazolium-based synthetic chloride and calcium transporters in bacterial membranes

Abstract

Herein, we present the first example of a benzimidazolium-based artificial transmembrane chloride transporter and a synthetic calcium ionophore that can regulate intracellular calcium concentrations in bacteria.

Phenylethynylbenzyl-Modified Biguanides Inhibit Pancreatic Cancer Tumor Growth

“…Phenylethynylbenzyl (PEB) -disubstituted imidazolium and benzimidazolium were shown to self-assemble inside phospholipid membranes and form stable channels through π-π interactions (Figure 1A) 13 . The transport of protons and ions through these open channels induced membrane perturbation, depolarization and bacterial death.…”

“…The transport of protons and ions through these open channels induced membrane perturbation, depolarization and bacterial death. Even if the PEB -disubstituted benzimidazolium salts were very active on bacterial membranes, their potential as mitochondrial membrane perturbators was not further explored because of their high toxicity on red blood cells (HC 50 at 0.15 mM) [13][14] . The replacement of one PEB unit with a phenyl or a methyl group resulted in less toxic compounds (HC 50 at 1 mM for the benzyl and 150 mM for the methyl substituent), forming more compact aggregates in the membranes.…”

“…In agreement, it has been shown that metformin exert its anti-cancer activity at least in part by perturbing mitochondrial respiration 7, 12 . We have actively investigated the membrane perturbation properties of synthetic amphiphilic cationic ion transporters and antibiotics, including derivatives of phenylethynylbenzyl (PEB) -disubstituted imidazolium and benzimidazolium salts. We have demonstrated that the activities of these organic salts in artificial phospholipid bilayers or living prokaryotic and eukaryotic cells were the results of membrane penetration, self-assembly and partition 13 . Since all the studied organic salts containing a PEB unit in their structure were active on bacterial membranes and that mitochondria are essentially ancient bacteria trapped in eukaryotic cells, we reasoned that conjugating biguanides with the PEB unit could improve metformin's cellular/mitochondrial uptake.…”

Antimicrobial and Antibiofilm Activity of Disubstituted Bis‐benzimidazolium Salts

“…[11,12] Previous studies by our group have shown that the addition of two phenylethynylbenzyl (PEB) arms to ab enzimidazolium cation (Figure1)r esulted in the formation of self-assembled channels in the phospholipid membranes. [13] We previously showedt hat bis-benzimidazolium salts 3a-c have the ability of inducing electrolytici mbalance andd isrupting the integrity and potential of planktonic bacterial membranes. [14] Herein, we were interested to see how the replacement of the PEB arm The increased prevalence of antibiotic-resistantb acteria is a critical issue for human health.…”

“…Previous studies by our group have shown that the addition of two phenylethynylbenzyl (PEB) arms to a benzimidazolium cation (Figure ) resulted in the formation of self‐assembled channels in the phospholipid membranes . We previously showed that bis‐benzimidazolium salts 3 a – c have the ability of inducing electrolytic imbalance and disrupting the integrity and potential of planktonic bacterial membranes .…”