On August 19, 2022, York, Edward; McNaughton, Daniel A.; Roseblade, Ariane; Cranfield, Charles G.; Gale, Philip A.; Rawling, Tristan published an article.Application of 102-07-8 The title of the article was Structure-Activity Relationship and Mechanistic Studies of Bisaryl Urea Anticancer Agents Indicate Mitochondrial Uncoupling by a Fatty Acid-Activated Mechanism. And the article contained the following:
Targeting the cancer cell mitochondrion is a promising approach for developing novel anticancer agents. The exptl. anticancer agent N,N’-bis(3,5-dichlorophenyl)urea (SR4) induces apoptotic cell death in several cancer cell lines by uncoupling mitochondrial oxidative phosphorylation (OxPhos) using a protein-free mechanism. However, the precise mechanism by which SR4 depolarizes mitochondria is unclear because SR4 lacks an acidic functional group typically found in protein-independent uncouplers. Recently, it was shown that structurally related thioureas can facilitate proton transport across lipid bilayers by a fatty acid-activated mechanism, in which the fatty acid acts as the site of protonation/deprotonation and the thiourea acts as an anion transporter that shuttles deprotonated fatty acids across the phospholipid bilayer to enable proton leak. In this paper, we show that SR4-mediated proton transport is enhanced by the presence of free fatty acids in the lipid bilayer, indicating that SR4 uncouples mitochondria through the fatty acid-activated mechanism. This mechanistic insight was used to develop a library of substituted bisaryl ureas for structure-activity relationship studies and subsequent cell testing. It was found that lipophilic electron-withdrawing groups on bisaryl ureas enhanced electrogenic proton transport via the fatty acid-activated mechanism and had the capacity to depolarize mitochondria and reduce the viability of MDA-MB-231 breast cancer cells. The most active compound in the series reduced cell viability with greater potency than SR4 and was more effective at inhibiting ATP production The experimental process involved the reaction of 1,3-Diphenylurea(cas: 102-07-8).Application of 102-07-8
The Article related to structure bisaryl urea cancer mitocondrial uncoupling fatty acid, Pharmacology: Structure-Activity and other aspects.Application of 102-07-8
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