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; Miguel Martin; Mar Roldan; Susana Rocha; Herlinde De Keersmaecker; Johan Hofkens; Juan M. Cuerva; Angel Orte

doi:10.20944/preprints202012.0358.v1

A peer-reviewed article of this Preprint also exists.

Ripoll, C.; Herrero-Foncubierta, P.; Puente-Muñoz, V.; Gonzalez-Garcia, M.C.; Miguel, D.; Resa, S.; Paredes, J.M.; Ruedas-Rama, M.J.; Garcia-Fernandez, E.; Martin, M.; Roldan, M.; Rocha, S.; De Keersmaecker, H.; Hofkens, J.; Cuerva, J.M.; Orte, A. Chimeric Drug Design with a Noncharged Carrier for Mitochondrial Delivery. Pharmaceutics 2021, 13, 254. Ripoll, C.; Herrero-Foncubierta, P.; Puente-Muñoz, V.; Gonzalez-Garcia, M.C.; Miguel, D.; Resa, S.; Paredes, J.M.; Ruedas-Rama, M.J.; Garcia-Fernandez, E.; Martin, M.; Roldan, M.; Rocha, S.; De Keersmaecker, H.; Hofkens, J.; Cuerva, J.M.; Orte, A. Chimeric Drug Design with a Noncharged Carrier for Mitochondrial Delivery. Pharmaceutics 2021, 13, 254.

DOI: 10.3390/pharmaceutics13020254

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 thiophene group as mitochondrial carrier for drugs and fluorescent markers, based on a new concept of nonprotonable, noncharged transporters. We implemented this concept in a medicinal chemistry application by developing an anti-tumoral, metabolic chimeric drug, based on 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-aimed drugs.

Keywords

Subject

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Chimeric Drug Design with a Noncharged Carrier for Mitochondrial Delivery

Abstract

Keywords

Subject

Comments (0)