ArticleChemical science2020
Aryl urea substituted fatty acids: a new class of protonophoric mitochondrial uncoupler that utilises a synthetic anion transporter.
Article in Chemical science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
- Fatty acid-activated proton transporter SR4 prevents hepatic steatosis and metabolic alterations in diabetic mice by improving mitochondria function, energy balance and oxidative stress.Experimental and therapeutic medicine · 2026Article
- The role of transmembrane proton transport rates in mild mitochondrial uncoupling by arylamide substituted fatty acids.Chemical science · 2026Article
- The radical scavenging activity of 1-methyl-1,4-dihydronicotinamide: theoretical insights into the mechanism, kinetics and solvent effects.RSC advances · 2024Article
- Optimizing Niclosamide for Cancer Therapy: Improving Bioavailability via Structural Modification and Nanotechnology.Cancers · 2024Review
- The Novel Anticancer Aryl-Ureido Fatty Acid CTU Increases Reactive Oxygen Species Production That Impairs Mitochondrial Fusion Mechanisms and Promotes MDA-MB-231 Cell Death.International journal of molecular sciences · 2024Article
- Mechanistic Aspects of Biphenyl Urea-Based Analogues in Triple-Negative Breast Cancer Cell Lines.ACS pharmacology & translational science · 2024Article
- Noncoupled Mitochondrial Respiration as Therapeutic Approach for the Treatment of Metabolic Diseases: Focus on Transgenic Animal Models.International journal of molecular sciences · 2023Review
- Synthesis and mechanism of biological action of morpholinyl-bearing arylsquaramides as small-molecule lysosomal pH modulators.RSC advances · 2022Article
- The hydroperoxyl antiradical activity of natural hydroxycinnamic acid derivatives in physiological environments: the effects of pH values on rate constants.RSC advances · 2022Article
- Recent Advances in Bioactive Artificial Ionophores.Chembiochem : a European journal of chemical biology · 2021Review
- Exploring the therapeutic potential of mitochondrial uncouplers in cancer.Molecular metabolism · 2021Review
- Towards the Application of Supramolecular Self-Associating Amphiphiles as Next-Generation Delivery Vehicles.Molecules (Basel, Switzerland) · 2020Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Respiring mitochondria establish a proton gradient across the mitochondrial inner membrane (MIM) that is used to generate ATP. Protein-independent mitochondrial uncouplers collapse the proton gradient and disrupt ATP production by shuttling protons back across the MIM in a protonophoric cycle. Continued cycling relies on the formation of MIM-permeable anionic species that can return to the intermembrane space after deprotonation in the mitochondrial matrix. Previously described protonophores contain acidic groups that are part of delocalised π-systems that provide large surfaces for charge delocalisation and facilitate anion permeation across the MIM. Here we present a new class of protonophoric uncoupler based on aryl-urea substituted fatty acids in which an acidic group and a π-system are separated by a long alkyl chain. The aryl-urea group in these molecules acts as a synthetic anion receptor that forms intermolecular hydrogen bonds with the fatty acid carboxylate after deprotonation. Dispersal of the negative charge across the aryl-urea system produces lipophilic dimeric complexes that can permeate the MIM and facilitate repeated cycling. Substitution of the aryl-urea group with lipophilic electron withdrawing groups is critical to complex lipophilicity and uncoupling activity. The aryl-urea substituted fatty acids represent the first biological example of mitochondrial uncoupling mediated by the interaction of a fatty acid and an anion receptor moiety,
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.