Antioxidative and Neuroprotective Effects of the Cytochalasans From Endophytes

Six 10-indolyl-cytochalasans, chaetoglobosin F (1), chaetoglobosin F-ex (2), chaetoglobosin E (3), cytoglobosin A (4), penochalasin C (5), and isochaetoglobosin D (6), and 2 10-phenyl-cytochalasans, cytochalasin H (7) and 18-methoxycytochalasin J (8) were isolated from 2 plant endophytes, Chaetomiun globosum WQ and Phomopsis sp. IFB-E060, respectively. These cytochalasans were investigated with radical-scavenging activity assay and hydrogen peroxide (H2O2)/N-methyl-4-phenylpyridinium iodide (MPP+)-induced pheochromocytoma cell line 12 (PC12) cell models, respectively. Results showed that 7 compounds had antioxidative effects except 5, with scavenging 2,2-diphenyl-1-picrylhydrazyl radical effect 1 = 6= 7 > 2> 4 = 3 > 8 and scavenging 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical effect 1 = 6 = 7 > 2 > 3 > 8 > 4. They could also inhibit H2O2/MPP+-induced damage in PC12 cells by increasing cell viability and decreasing lactate dehydrogenase release. Compounds 1, 6, and 7 exhibited the strongest antioxidative potencies, which are more potent than vitamin E. Additionally, antioxidative and neuroprotective effects of 1 similar to 8 showed some structure-activity relationship. These findings would be useful for looking for cytochalasin-related new lead compounds or drugs to prevent and treat Parkinson's disease.