Synthetic Anionophores Enhance the Activity of Anionic Drugs
Krystyna Maslowska-Jarzyna1, Bartłomiej Zawada1, Radosław Stachowiak2
1Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Warsaw, Poland.
Abstract:
Lipid bilayers pose a major barrier to the passive diffusion of anionic species, including many carboxylate-containing drugs. This limited membrane permeability can reduce drug efficacy and allow bacteria to deploy various defense mechanisms. In this study, we show that small synthetic anionophores can significantly enhance the antibacterial activity of anionic antibiotics by accelerating their transmembrane transport. In liposomes, these anionophores increase the transmembrane transport rate of carboxylate drugs by over two orders of magnitude, even when present in catalytic amounts. In bacteria, the same artificial carriers amplify the activity of clinically used anionic antibiotics, markedly enhancing their antimicrobial activity against both Gram-positive and Gram-negative strains. Notably, the extent of this activity enhancement directly correlates with the carrier-induced increase in drug permeability. These results demonstrate that synthetic anion carriers can improve not only membrane permeability but also the therapeutic performance of anionic drugs, offering a promising strategy for overcoming permeability-related resistance in drug design.
Related Concept Videos
01:17Ion Exchange
01:17Pore Transport and Ion-Pair Transport
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct microscopic...
01:14Active Transport
Primary active transporters, like Na+, K+ and -ATPase, directly utilize ATP to move ions across the membrane. These transporters play significant roles in various physiological processes. For instance, Na+, K+ and -ATPase maintain...
01:26Enhanced Elimination of Poison
Antidotes serve a crucial role in counteracting the effects of poison by inhibiting enzymes responsible for producing harmful drug metabolites. In some cases, these toxic metabolites can be neutralized by endogenous cosubstrates, which are maintained at specific concentrations to prevent interaction with cellular macromolecules and subsequent cell death.
Renal excretion is the...
01:22Drug Elimination by Renal Route: Tubular Reabsorption
01:17Antidotes
Specific antidotes operate by inhibiting the enzymes that control biochemical pathways, reducing the production of harmful metabolites.
An example of an antidote is atropine, which counteracts the detrimental effects of cholinesterase inhibitors. It achieves this by deactivating muscarinic receptors,...