LIGNANS INTERFERING WITH 5-ALPHA-DIHYDROTESTOSTERONE BINDING TO HUMANSEX HORMONE-BINDING GLOBULIN

The natural lignans (-)-3,4-divanillyltetrahydrofuran (1), (-)-mataire sinol (2), (-)-secoisolariciresinol(3), (+/-)-enterolactone (4), (+/-) -enterodiol (5), and nordihydroguaiaretic acid (NDGA) (6) reduce the b inding of H-3-labeled 5 alpha-dihydrotestosterone (DHT) to human sex h ormone-binding globulin (SHBG). (-)-3,4-Divanillyltetrahydrofuran (1) has the highest binding affinity (a(K) = 3.2 +/- 1.7 x 10(6) M-1) of a ll lignans investigated so far; the reversibility of its binding and a double reciprocal plot suggest a competitive inhibition of the SHBG-D HT interaction. Increasing hydrophobity in the aliphatic part of the l ignans (butane-1,4-diol-butanolide-tetrahydrofuran structures) leads t o higher binding affinity. In the aromatic part, a 3-methoxy-4-hydroxy substitution pattern is most effective for binding to SHBG.