1. Chimeric Drug Design with a Noncharged Carrier for Mitochondrial Delivery.
- Author
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Ripoll, Consuelo, Herrero-Foncubierta, Pilar, Puente-Muñoz, Virginia, Gonzalez-Garcia, M. Carmen, Miguel, Delia, Resa, Sandra, Paredes, Jose M., Ruedas-Rama, Maria J., Garcia-Fernandez, Emilio, Roldan, Mar, Rocha, Susana, De Keersmaecker, Herlinde, Hofkens, Johan, Martin, Miguel, Cuerva, Juan M., Orte, Angel, and Kopecka, Joanna
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PYRUVATE dehydrogenase kinase , *DRUG design , *MITOCHONDRIA , *DRUG carriers , *PHARMACEUTICAL chemistry - Abstract
Recently, 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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