Aza‐CGP37157‐lipoic hybrids designed as novel Nrf2‐inducers and antioxidants exert neuroprotection against oxidative stress and show neuroinflammation inhibitory properties

• Published in: Drug development research Vol. 81; no. 3; pp. 283 - 294
• Main Authors: Michalska, Patrycja, Tenti, Giammarco, Satriani, Michelle, Cores, Angel, Ramos, María Teresa, García, Antonio G., Menéndez, José Carlos, León, Rafael
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.05.2020; Wiley Subscription Services, Inc
• Subjects: Antioxidants; anti‐inflammatory activity; Calcium (mitochondrial); Calcium ions; Hybrids; Inflammation; Lipoic acid; Mitochondria; Na+/Ca2+ exchanger; Neuroprotection; Nrf2 induction; Oxidative stress; Properties (attributes); radical scavenging; Scavenging; radical scavenging; neuroprotection; Nrf2 induction; anti-inflammatory activity
• ISSN: 0272-4391; 1098-2299
• DOI: 10.1002/ddr.21618

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.