Neuroprotective and Antioxidant Effects of Novel Benzofuran-2-Carboxamide Derivatives.
10.4062/biomolther.2015.030
- Author:
Jungsook CHO
1
;
Chowee PARK
;
Youngmun LEE
;
Sunyoung KIM
;
Shambhunath BOSE
;
Minho CHOI
;
Arepalli Sateesh KUMAR
;
Jae Kyung JUNG
;
Heesoon LEE
Author Information
1. College of Pharmacy, Dongguk University-Seoul, Goyang 410-820, Republic of Korea.
- Publication Type:In Vitro ; Original Article
- Keywords:
Neuroprotection;
Excitotoxicity;
Reactive oxygen species;
Antioxidant activity;
Benzofuran-2-carboxamide derivatives
- MeSH:
Animals;
Antioxidants*;
Biological Assay;
Brain;
Lipid Peroxidation;
Mass Screening;
Memantine;
N-Methylaspartate;
Neurons;
Neuroprotective Agents;
Rats;
Reactive Oxygen Species;
Structure-Activity Relationship
- From:Biomolecules & Therapeutics
2015;23(3):275-282
- CountryRepublic of Korea
- Language:English
-
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.
