Brassinolide activities of 2α,3α-diols versus 3α,4α-diols in the bean second internode bioassay: Explanation by molecular modeling methods

In general, the structural requirements postulated for a high brassinolide activity are: 2α,3α-diol, 6-ketone or better 7-oxalactone in B-ring, A/B trans fused ring junction, a cis C-22,C-23-diol preferentially with RR configurations, and a C-24 methyl or ethyl substituent [Takatsuto S, Yazawa N, Ikekawa N, Takematsu T, Takeuchi Y, Koguchi M. Structure–activity relationship of brassinosteroids. Phytochemistry 1983;22:2437–41; Thompson MJ, Meudt WJ, Mandava NB, Dutky SR, Lusby WR, Spaulding DW. Synthesis of brassinosteroids and relationship of structure to plant growth-promoting effects. Steroids 1982;39:89–105]. We found that the 3α,4α-diols 4, 6 and 8 are more active than the 2α,3α-diols 3, 5 and 7 [Šíša M, Buděšínský M, Kohout L. Synthesis of 7a-homo and 7a,7b-dihomo-5α-cholestane analogues of brassinolide. Collect Czech Chem Commun 2003;68:2171–89]. This fact is in strong contrast with the structure requirements mentioned above. Our hypothesis suggests that the lower activity of 2α,3α-diols and/or the higher activity of 3α,4α-diols could be explained by twisting and distortion of the molecule due to the seven- or eight-membered B-ring and also by the position of a carbonyl group relative to the A-ring diol. 3D-SAR computer methodologies as alignments and overlaps of GRID maps and 3D-QSAR analysis GRID-GOLPE (CoMFA-like) were used as an effort to explain the higher bioactivity of 3α,4α-diols 4, 6 and 8 in comparison with the 2α,3α-diols 3, 5 and 7 of B-ring enlarged brassinosteroids.