Ripoll, ConsueloHerrero-Foncubierta, PilarPuente-Muñoz, VirginiaGonzalez-Garcia, M CarmenMiguel, DeliaResa, SandraParedes, Jose MRuedas-Rama, Maria JGarcia-Fernandez, EmilioRoldan, MarRocha, SusanaDe Keersmaecker, HerlindeHofkens, JohanMartin, MiguelCuerva, Juan MOrte, Angel2025-01-072025-01-072021-02-121999-4923https://hdl.handle.net/10668/28415Recently, it was proposed that the thiophene ring is capable of promoting mitochondrial accumulation when linked to fluorescent markers. As a noncharged group, thiophene presents several advantages from a synthetic point of view, making it easier to incorporate such a side moiety into different molecules. Herein, we confirm the general applicability of the thiophene group as a mitochondrial carrier for drugs and fluorescent markers based on a new concept of nonprotonable, noncharged transporter. We implemented this concept in a medicinal chemistry application by developing an antitumor, metabolic chimeric drug based on the pyruvate dehydrogenase kinase (PDHK) inhibitor dichloroacetate (DCA). The promising features of the thiophene moiety as a noncharged carrier for targeting mitochondria may represent a starting point for the design of new metabolism-targeting drugs.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/antitumor agentsfluorescence lifetime imagingmedicinal chemistrymetabolic drugmitochondrial carrierresearch article33673228open access10.3390/pharmaceutics13020254PMC7918843https://www.mdpi.com/1999-4923/13/2/254/pdfhttps://pmc.ncbi.nlm.nih.gov/articles/PMC7918843/pdf