title: Synthesis and biological evaluation of novel marine-derived indole-based 1,2,4-oxadiazoles derivatives as multifunctional neuroprotective agents.
abstract: Phidianidines (1), isolated from the marine opisthobranch mollusk Phidiana militaris, present the first example of natural products possessing an 1,2,4-oxadiazole ring system and show various bioactivities. However, the structure-activity relationship study related to 1 has not been reported yet. As our ongoing effect toward marine-derived potential neuroprotective agents, a series of phidianidine-based derivatives have been synthesized and evaluated for neuroprotective effects against amyloid-β25-35 (Aβ25-35)-, hydrogenperoxide (H2O2)-, and oxygen-glucose deprivation (OGD)-induced neurotoxicity in SH-SY5Y cells. The bioassay results indicated that some of analogs, especially 2q and 2r, exhibited good in vitro neuroprotective effects in the above three screening models. The preliminary SAR study indicated that substituent groups introduced to the benzene ring play a crucial role in their bioactivity. In particular, the linear alkoxy group at 4-position favors the neuroprotective activity, while a bulky group could lead the activity decrease or loss. These findings could provide an alternative strategy for the development of novel indole-based 1,2,4-oxadiazole derivatives for the treatment of Alzheimer's disease.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang High-Tech Park, Shanghai 201203, PR China.
authors.forename: Cheng-Shi
authors.initials: CS
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang High-Tech Park, Shanghai 201203, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang High-Tech Park, Shanghai 201203, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang High-Tech Park, Shanghai 201203, PR China.
authors.forename: Jing-Xu
authors.initials: JX
authors.lastname: Gong
authors.affiliation: Jiangsu Kanion Pharmaceutical Co. Ltd, Lianyungang 222001, PR China.
authors.forename: Zhen-Zhong
authors.initials: ZZ
authors.lastname: Wang
authors.affiliation: Jiangsu Kanion Pharmaceutical Co. Ltd, Lianyungang 222001, PR China. Electronic address: wzhzh-nj@163.net.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang High-Tech Park, Shanghai 201203, PR China. Electronic address: hzhang@simm.ac.cn.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang High-Tech Park, Shanghai 201203, PR China. Electronic address: ywguo@simm.ac.cn.
authors.forename: Yue-Wei
authors.initials: YW
authors.lastname: Guo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008974:Mollusca; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D007211:Indoles; D018696:Neuroprotective Agents; D010069:Oxadiazoles; C030374:indole
keywords: 1,2,4-Oxadiazole derivatives; Amyloid-β-peptide; Neuroprotective activity; Oxygen–glucose deprivation; Phidianidines