title: Neuroprotective and antioxidant effects of novel benzofuran-2-carboxamide derivatives.
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 μM 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 μM concentration. In addition to 1f, compound 1j (with -OH substitution at R3 position) also showed marked anti-excitotoxic effects at both 100 and 300 μM 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.
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang 410-820.
authors.forename: Jungsook
authors.initials: J
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang 410-820.
authors.forename: Chowee
authors.initials: C
authors.lastname: Park
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang 410-820.
authors.forename: Youngmun
authors.initials: Y
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang 410-820.
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang 410-820.
authors.forename: Shambhunath
authors.initials: S
authors.lastname: Bose
authors.affiliation: Collegy of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Minho
authors.initials: M
authors.lastname: Choi
authors.affiliation: Collegy of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Arepalli Sateesh
authors.initials: AS
authors.lastname: Kumar
authors.affiliation: Collegy of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Jung
authors.affiliation: Collegy of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Heesoon
authors.initials: H
authors.lastname: Lee
keywords: Antioxidant activity; Benzofuran-2-carboxamide derivatives; Excitotoxicity; Neuroprotection; Reactive oxygen species