The Structure-Activity Relationships of Flaxseed Lignan, Secoisolariciresinol

It is well known that the physiological activities of compounds are affected by their molecular structures. Hence, it is very important for the risk assessment of environmental chemicals such as PCDD and PCDF to evaluate structure-activity relationships (SAR). For precise analysis of SAR, the compounds should be stereoselectively synthesized. In this paper, we evaluated SAR of flaxseed lignan, secoisolariciresinol (SECO). SECO has many physiological effects such as immunostimulatory activity, antioxidant activity, and estrogenic activity. In addition, we first achieved the stereoselective synthesis of meso-SECO and optically active SECOs. Hence, SECO is a very good example for examining SAR. Optically active (+)and (–)-SECO, and meso-SECO were synthesized and various physiological functions were compared. At first, the immunostimulatory effects were examined. (+)and (–)-SECO accelerated IgM production of human hybridoma cells, however, meso-SECO did not. However meso-SECO showed cytotoxic activity against human breast cancer MCF-7 cells, (–)-SECO slightly stimulated the cell. This means that estrogenic activity of SECO derived from only (–)-SECO. Although (–)-SECO stimulated adiponectin production of 3T3-L1 adipose cells, (+)and meso-SECO suppressed the production. These facts suggested that slight difference in the structure of SECO affects the physiological activity.