Ripoll, ConsueloHerrero-Foncubierta, PilarPuente-Muñoz, VirginiaGonzalez-Garcia, M. CarmenMiguel, DeliaResa, SandraParedes, Jose M.Ruedas-Rama, Maria J.Garcia-Fernandez, EmilioRoldan, MarRocha, SusanaDe Keersmaecker, HerlindeHofkens, JohanMartin, MiguelCuerva, Juan M.Orte, Angel2022-08-042022-08-042021-02-12Ripoll C, Herrero-Foncubierta P, Puente-Muñoz V, Gonzalez-Garcia MC, Miguel D, Resa S, et al. Chimeric Drug Design with a Noncharged Carrier for Mitochondrial Delivery. Pharmaceutics. 2021 Feb 12;13(2):254http://hdl.handle.net/10668/3874Recently, 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Antitumor agentsFluorescence lifetime imagingMedicinal chemistryMetabolic drugMitochondrial carrierAntineoplásicosQuímica farmacéuticaActivación metabólicaTiofenosMitocondriasMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Pharmacology::Chemistry, PharmaceuticalMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::MitochondriaMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Sulfur Compounds::ThiophenesMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic AgentsMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolismresearch article33673228Acceso abierto10.3390/pharmaceutics130202541999-4923PMC7918843