Biomol Ther.  2015 May;23(3):275-282. 10.4062/biomolther.2015.030.

Neuroprotective and Antioxidant Effects of Novel Benzofuran-2-Carboxamide Derivatives

• Cho J
• Park C
• Lee Y
• Kim S
• Bose S
• Choi M
• Kumar AS
• Jung JK
• Lee H

• KMID: 2380338
• DOI: http://doi.org/10.4062/biomolther.2015.030

Abstract

In the present study, we synthesized a series of novel 7-methoxy-N-(substituted phenyl)benzofuran-2-carboxamide derivatives in moderate to good yields and evaluated their neuroprotective and antioxidant activities using primary cultured rat cortical neuronal cells and in vitro cell-free bioassays. Based on our primary screening data with eighteen synthesized derivatives, nine compounds (1a, 1c, 1f, 1i, 1j, 1l, 1p, 1q and 1r) exhibiting considerable protection against the NMDA-induced excitotoxic neuronal cell damage at the concentration of 100 muM were selected for further evaluation. Among the selected derivatives, compound 1f (with -CH3 substitution at R2 position) exhibited the most potent and efficacious neuroprotective action against the NMDA-induced excitotoxicity. Its neuroprotective effect was almost comparable to that of memantine, a well-known NMDA antagonist, at 30 muM concentration. In addition to 1f, compound 1j (with -OH substitution at R3 position) also showed marked anti-excitotoxic effects at both 100 and 300 muM concentrations. These findings suggest that -CH3 substitution at R2 position and, to a lesser degree, -OH substitution at R3 position may be important for exhibiting neuroprotective action against excitotoxic damage. Compound 1j was also found to scavenge 1,1-diphenyl-2-picrylhydrazyl radicals and inhibit in vitro lipid peroxidation in rat brain homogenate in moderate and appreciable degrees. Taken together, our structure-activity relationship studies suggest that the compound with -CH3 substitution at R2 and -OH substitution at R3 positions of the benzofuran moiety might serve as the lead exhibiting potent anti-excitotoxic, ROS scavenging, and antioxidant activities. Further synthesis and evaluation will be necessary to confirm this possibility.

Keyword

Neuroprotection; Excitotoxicity; Reactive oxygen species; Antioxidant activity; Benzofuran-2-carboxamide derivatives

MeSH Terms

Animals
Antioxidants*
Biological Assay
Brain
Lipid Peroxidation
Mass Screening
Memantine
N-Methylaspartate
Neurons
Neuroprotective Agents
Rats
Reactive Oxygen Species
Structure-Activity Relationship
Antioxidants
Memantine
N-Methylaspartate
Neuroprotective Agents
Reactive Oxygen Species