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Aza-CGP37157-lipoic hybrids designed as novel Nrf2-inducers and antioxidants exert neuroprotection against oxidative stress and show neuroinflammation inhibitory properties |
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| Authors: | Patrycja Michalska Giammarco Tenti Michelle Satriani Angel Cores María Teresa Ramos Antonio G García José Carlos Menéndez Rafael León |
| Institution: | 1. Instituto Teófilo Hernando y Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain
Instituto de Investigación Sanitaria, Servicio de Farmacología Clínica, Hospital Universitario de la Princesa, Madrid, Spain;2. Unidad de Química Orgánica y Farmacéutica, Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense, Madrid, Spain;3. Instituto Teófilo Hernando y Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain Unidad de Química Orgánica y Farmacéutica, Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense, Madrid, Spain;4. Instituto Teófilo Hernando y Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain |
| Abstract: | Two multitarget hybrids, derived from an aza-analogue of CGP37157, a mitochondrial Na+/Ca2+ exchanger antagonist, and lipoic acid were designed in order to combine in a single molecule the antioxidant and Nrf2 induction properties of lipoic acid and the neuroprotective activity of CGP37157. The hybrid derivatives showed Nrf2 induction and radical scavenging properties, leading to a good neuroprotective profile against oxidative stress, together with an interesting antineuroinflammatory activity. The results obtained show differences in activity depending on the configuration of the chiral center of LA. |
| Keywords: | anti-inflammatory activity neuroprotection Nrf2 induction radical scavenging |