Interaction of lignans with human sex hormone binding globulin (SHBG)

Abstract

Lignans bind to sex hormone-binding globulin (SHBG). The lignan with the highest binding affinity is (±)-3,4-divanillyltetrahydrofuran. In a double Stobbe condensation - without use of protecting groups - a wide variety of lignans with different substitution pattern in the aromatic and aliphatic part of the molecule was synthesized. These lignans were tested in a SHBG-binding assay which allowed to deduce the following relationship between structure and activity: 1) (±)-diastereoisomers are more active than meso compounds 2.) the 4-hydroxy-3-methoxy (guajacyl) substitution pattern in the aromatic part is most effective 3.) the activity increases with the decline in polarity of the aliphatic part of the molecule.