Marine macroalgal sulfated fucose-containing polysaccharides,like fucoidan,have drawn significant attention due to their biotechnological potentials,such as anti-cancer,antioxidant,and anti-cholinesterase activities.T...Marine macroalgal sulfated fucose-containing polysaccharides,like fucoidan,have drawn significant attention due to their biotechnological potentials,such as anti-cancer,antioxidant,and anti-cholinesterase activities.The fucoidan derived from brown macroalgae Sargassum angustifolium species(FSA)was investigated for its cytotoxic effects and alterations in cell proliferation,and cell cycle-related gene expression in the present study occurred on NB4 cell line.The results showed that FSA would induce p53,p21,pro-apoptotic genes and increase expression of the p15 gene as a cell arrest marker.Also,FSA inhibited the anti-apoptotic effect of the Bcl-2 gene and decreased dnmt-1 gene expression.FSA significantly exhibited potent 2,2-diphenyl-1-picrylhydrazyl(DPPH)radical scavenging activity(p<0.05)with an IC_(50) value of 0.157 mg/mL and showed moderate anti-acetylcholinesterase activity with an IC_(50) value of 1.20μg/mL.These results indicated the potential of FSA for the development of therapeutic or preventive agents of cancer and Alzheimer’s disease mainly through cytotoxic effect and AChE(acetylcholinesterase)inhibition as well as additional antioxidant capacities.展开更多
A new series of physostigmine analogues 3a--3j with modifications at the C3a and C5 positions was de- signed and synthesized. Bioassay of the synthetic analogues 3a--3j, along with the previous synthesized C3a-ethyl-C...A new series of physostigmine analogues 3a--3j with modifications at the C3a and C5 positions was de- signed and synthesized. Bioassay of the synthetic analogues 3a--3j, along with the previous synthesized C3a-ethyl-C5-triazole physostigmine analogues laJlg and 2a--2j was performed, which indicates that the replace- ment of the carbamoyl moiety of C3a-ethyl-C5-triazole analogues 1 and 2 with a triazole moiety decreased acetyl- cholinesterase（AchE） inhibitory activity, whereas the introduction of heterocycles into the triazole ring increased both AChE and butyrylcholinesterase（BchE） inhibitory activities. Structure-activity relationship（SAR） studies of C3a-methyl-C5-triazole analogues 3 reveal the C3a-methyl substituent is important for AChE and BChE inhibition and the introduction of a second ionizable N center improved the binding of the synthetic analogues to both AChE and BChE.展开更多
基金The Iran National Science Foundation under contract No. 96015033
文摘Marine macroalgal sulfated fucose-containing polysaccharides,like fucoidan,have drawn significant attention due to their biotechnological potentials,such as anti-cancer,antioxidant,and anti-cholinesterase activities.The fucoidan derived from brown macroalgae Sargassum angustifolium species(FSA)was investigated for its cytotoxic effects and alterations in cell proliferation,and cell cycle-related gene expression in the present study occurred on NB4 cell line.The results showed that FSA would induce p53,p21,pro-apoptotic genes and increase expression of the p15 gene as a cell arrest marker.Also,FSA inhibited the anti-apoptotic effect of the Bcl-2 gene and decreased dnmt-1 gene expression.FSA significantly exhibited potent 2,2-diphenyl-1-picrylhydrazyl(DPPH)radical scavenging activity(p<0.05)with an IC_(50) value of 0.157 mg/mL and showed moderate anti-acetylcholinesterase activity with an IC_(50) value of 1.20μg/mL.These results indicated the potential of FSA for the development of therapeutic or preventive agents of cancer and Alzheimer’s disease mainly through cytotoxic effect and AChE(acetylcholinesterase)inhibition as well as additional antioxidant capacities.
基金Supported by the National Natural Science Foundation of China（No.21202209）, the National Science ＆ Technology Major Project of China（No.2011ZX09401-304）, the Fundamental Research Funds for the Central Universities, China （No.CQDXWL-2012-131） and the Natural Science Foundation Project of Chongqing Science and Technology Commission, China（No.cstc2012jjA10087）.
文摘A new series of physostigmine analogues 3a--3j with modifications at the C3a and C5 positions was de- signed and synthesized. Bioassay of the synthetic analogues 3a--3j, along with the previous synthesized C3a-ethyl-C5-triazole physostigmine analogues laJlg and 2a--2j was performed, which indicates that the replace- ment of the carbamoyl moiety of C3a-ethyl-C5-triazole analogues 1 and 2 with a triazole moiety decreased acetyl- cholinesterase（AchE） inhibitory activity, whereas the introduction of heterocycles into the triazole ring increased both AChE and butyrylcholinesterase（BchE） inhibitory activities. Structure-activity relationship（SAR） studies of C3a-methyl-C5-triazole analogues 3 reveal the C3a-methyl substituent is important for AChE and BChE inhibition and the introduction of a second ionizable N center improved the binding of the synthetic analogues to both AChE and BChE.
