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.

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.

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Chimeric Drug Design with a Noncharged Carrier for Mitochondrial Delivery

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