ABSTRACT
The structure of fibrauretin made by our lab was modified. Fibrauretin was demethylated at 9-site under high temperature pyrolysis at 160℃-180℃ and was reacted with a series of acid chlorides. Twele derivatives of fibrauretin were obtained. The structure of each derivative was determined by1H-NMR and13C-NMR. The derivatives were 9-O-benzoyl-fibrauretin, 9-O-( 2-methylbenzoyl)-fibrauretin, 9-O-( 4-methylbenzoyl)-fibrauretin, 9-O-(3, 5-dimethylbenzoyl)-fibrauretin, 9-O-(4-(chloromethyl) benzoyl)-fibrauretin and other derivatives. The 12 derivatives are all new chemical compounds. Taking ATCI as substrate,the inhibitory activity on acetylcholinesterase (AChE) from the head of flies of the fibrauretin and its derivatives were screened. The results showed that most of the derivatives had improved their inhibitory activity on AChE through esterification reaction. Compounds 9-O-(4-methylbenzoyl)-fibrauretin, 9-O-(3,5-dimethylbenzoyl)-fibrauretinand 9-O-(4-(chloromethyl)benzoyl)-fibrauretin had significant inhibitory effect on AChE,and the inhibitory activity was stronger than the that of donepezil.
ABSTRACT
Objective To investigate the protective effect of fibrauretin injection against acute lung injury induced by lipopolysaccharide (LPS) in mice.Methods Seventy-two healthy male adult Kunming mice were randomly divided into 6 goups:normal control group,LPS group (intratracheal instilation of 5 mg/kg of LPS),hydrocortisone group (intraperitoneal injection of 3.3 mg/kg of hydrocortisone,once daily for 3 days,and intratracheal instilation of 5 mg/kg of LPS on the 4th day) and low dose,medium dose and high dose of fibrauretin groups (intraperitoneal injection of 2,10 and 50 mg/kg of fibrauretin,respectively,once daily for 3 days,and intratracheal instilation of 5 mg/kg of LPS on the 4th day).The mice in each group were sacrificed by dislocation 24 h after intratracheal instilation of LPS.The lung tissues of partial mice in each group were extracted and weighed to calculate the lung coefficients,and bronchoalveolar lavage (BAL) was performed in partial mice in each group to collect the BALF for counting the inflammatory cells.Results The lung cofficients of mice in LPS group were significantly higher than those in the normal control group (P＜0.05).The lung cofficients of mice in hydrocortisone group,low dose,medium dose and high dose of fibrauretin groups were significantly lower than those in LPS group (P ＜ 0.05).For the percentage of inflammatory cells in BALF and the percentage of neutrophils in inflammatory cells,LPS group was significantly higher than the normal control group (P＜0.01),and compared with LPS group,hydrocortisone group,low dose,medium dose and high dose of fibrauretin groups were significantly decreased (P＜0.01).Conclusion Fibrauretin injection can significantly ameliorate the inflammatory reaction degree in mice with acute lung injury induced by LPS.