Pharmaceutics (Feb 2021)

Chimeric Drug Design with a Noncharged Carrier for Mitochondrial Delivery

  • Consuelo Ripoll,
  • Pilar Herrero-Foncubierta,
  • Virginia Puente-Muñoz,
  • M. Carmen Gonzalez-Garcia,
  • Delia Miguel,
  • Sandra Resa,
  • Jose M. Paredes,
  • Maria J. Ruedas-Rama,
  • Emilio Garcia-Fernandez,
  • Mar Roldan,
  • Susana Rocha,
  • Herlinde De Keersmaecker,
  • Johan Hofkens,
  • Miguel Martin,
  • Juan M. Cuerva,
  • Angel Orte

DOI
https://doi.org/10.3390/pharmaceutics13020254
Journal volume & issue
Vol. 13, no. 2
p. 254

Abstract

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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.

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