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
Departamento de Fisicoquimica, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente, Facultad de Farmacia, Universidad de Granada, Campus Cartuja, 18071 Granada, Spain.
Departamento de Quimica Organica, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente, Facultad de Ciencias, Universidad de Granada, Campus Fuentenueva, 18071 Granada, Spain.
Pharmaceutics. 2021 Feb 12;13(2):254. doi: 10.3390/pharmaceutics13020254.
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.
最近有人提出，噻吩环与荧光标记物相连时能够促进线粒体积累。作为一个不带电荷的基团，从合成的角度来看，噻吩具有几个优点，使得将这样一个侧链部分纳入不同分子变得更容易。在此，我们基于不可质子化、不带电荷的转运体这一新概念，证实了噻吩基团作为药物和荧光标记物的线粒体载体的普遍适用性。我们通过开发一种基于丙酮酸脱氢酶激酶（PDHK）抑制剂二氯乙酸（DCA）的抗肿瘤代谢嵌合药物，将这一概念应用于药物化学领域。噻吩部分作为靶向线粒体的不带电荷载体的有前景的特性，可能代表了设计新型代谢靶向药物的一个起点。
