Recent Advances in Bioactive Artificial Ionophores

Abstract

Several life-threatening diseases, also known as 'Channelopathies' are linked to irregularities in ion transport proteins. Significant research efforts have fostered the development of artificial transport systems that facilitates to restore the functions of impaired natural transport proteins. Indeed, a few of these artificial ionophores demonstrate the rare combination of transmembrane ion transport and important biological activity, offering early promises of suitability in 'channel replacement therapy'. In this review, structural facets and functions of both cationophores and anionophores are discussed. Iono-phores that are toxic to various bacteria and yeast, could be exploited as antimicrobial agent. Nevertheless, few non-toxic ionophores offer the likelihood of treating a wide range of genetic diseases caused by the gene mutations. In addition, their ability to disrupt cellular homeostasis and to alter lysosomal pH endow ionophores as promising candidates for cancer treatment. Overall, critically outlining the advances in artificial ionophores in terms of in vitro ion transport, possible modes of action and biological activities enables us to propose possible future roadmaps in this research area.

A Pyridyl-Linked Benzimidazolyl Tautomer Facilitates Prodigious H+/Cl– Symport through a Cooperative Protonation and Chloride Ion Recognition

“…Synthetic molecules capable of transporting ions across lipid bilayer have been studied extensively over several years . Remarkable progress in the understanding of mutations in genes linked with the physiology of Cl – transport has led to the development of synthetic transporters as therapeutic modalities for cystic fibrosis, Bartter syndrome, and so on .…”

Structure – Bioactivity Relationship in Cyclic Peptoids: An Overview

“…[25][26][27] In the past few years, the term "channelopathy" was coined, indicating a number of pathologies related to malfunctioning ion transport proteins. [28] Thus, the search for synthetic ion transporters, capable to compensate such irregularities, has gained interest. [29] The presence of a macrocyclic scaffold provides a preorganized donor framework, ready to encapsulate the metallic guest, similar to crown ethers or cryptands.…”

“…In the past few years, the term “channelopathy” was coined, indicating a number of pathologies related to malfunctioning ion transport proteins [28] . Thus, the search for synthetic ion transporters, capable to compensate such irregularities, has gained interest [29] .…”

Supramolecular chemistry in lipid bilayer membranes

“…The field of "supramolecular medicinal chemistry", with particular focus on applications of anionophores, has been reviewed extensively, and readers are directed to recent reviews. 71,73,183 Before anionophores find their way from the lab to the clinic, there are arguably many hurdles to overcome, including optimising activity, ion selectivity, delivery and targeting, and toxicity. One of the often explored parameters in anionophore design is activity (typically the more active, the better), but as discussed previously, selectivity is also critical, because the presence of an anionophore will inevitably impact cellular homeostasis.…”