ABSTRACT
Low-molecular weight type I and II fucoidan derivatives with different sulfation patterns were designed and systematically synthesized from the corresponding common key intermediate and their anti-proliferative activities and apoptosis-inducing activities against human breast cancer (MCF-7) and human cervical epithelioid carcinoma (HeLa) cells were evaluated. Our results demonstrated that one of the type II fucoidan derivatives, 9, effectively reduced the number of viable MCF-7 and HeLa cells in a dose-dependent manner without causing cytotoxicity toward normal WI-38 cells, and that the anti-proliferative activity of 9 was comparable to that of fucoidan 2 isolated from Fucus vesiculosus. Moreover, it was found that both 2 and 9 exhibited similar apoptosis-inducing activities through activation of caspase-8 and -9 on MCF-7 and HeLa cells, respectively.
Subject(s)
Breast Neoplasms/drug therapy , Polysaccharides/chemical synthesis , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Apoptosis , Blotting, Western , Cell Line, Tumor , Cell Proliferation/drug effects , Cells, Cultured , Female , HeLa Cells , Humans , Immunoblotting , Microscopy, Fluorescence , Molecular Structure , Molecular Weight , Polysaccharides/chemistry , Polysaccharides/pharmacologyABSTRACT
Sulfated tetrafucosides with different sulfation patterns, and a non-sulfated tetrafucoside , were designed and systematically synthesized from the common key intermediate . In addition, their anti-proliferative activities and apoptosis-inducing activities against human breast cancer MCF-7 cells were evaluated. Our results demonstrated that the sulfated tetrafucosides reduced the number of MCF-7 cells in a dose-dependent manner, and of these, 3,4-O-sulfated type showed the highest anti-proliferative activity, comparable to the activity of fucoidan isolated from Fucus vesiculosus. Furthermore, it was revealed that both and exhibited apoptosis-inducing activities through activation of caspase-8 on MCF-7 cells.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Breast Neoplasms/drug therapy , Fucus/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Antineoplastic Agents/chemical synthesis , Breast Neoplasms/enzymology , Breast Neoplasms/pathology , Caspase 8/metabolism , Female , Humans , MCF-7 Cells , Polysaccharides/chemical synthesis , Sulfates/chemical synthesis , Sulfates/chemistry , Sulfates/pharmacologyABSTRACT
Design and synthesis of a boronic acid based artificial receptor which selectively and effectively bound to a neurotransmitter, l-DOPA (), in aqueous media. In addition, the synthetic receptor was found to effectively inhibit the DDC (l-DOPA decarboxylase) enzymatic reaction under physiological conditions.