Brassinolide activities of 2alpha,3alpha-diols versus 3alpha,4alpha-diols in the bean second internode bioassay: explanation by molecular modeling methods.
In general, the structural requirements postulated for a high brassinolide activity are: 2alpha,3alpha-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 3alpha,4alpha-diols 4, 6 and 8 are more active than the 2alpha,3alpha-diols 3, 5 and 7 [Sísa M, Budesínský M, Kohout L. Synthesis of 7a-homo and 7a,7b-dihomo-5alpha-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 2alpha,3alpha-diols and/or the higher activity of 3alpha,4alpha-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 3alpha,4alpha-diols 4, 6 and 8 in comparison with the 2alpha,3alpha-diols 3, 5 and 7 of B-ring enlarged brassinosteroids.
Sísa
Miroslav
M
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo n 2, 166 10, Prague 6, Czech Republic.
Vilaplana-Polo
Marc
M
Ballesteros
Carme Brosa
CB
Kohout
Ladislav
L
D001681:Biological Assay / Q000379:methods*; D060406:Brassinosteroids; D002777:Cholestanols / Q000737:chemistry / Q000378:metabolism*; D007887:Fabaceae / Q000378:metabolism*; D016018:Least-Squares Analysis; D008958:Models, Molecular; D008968:Molecular Conformation; D011083:Polycyclic Compounds / Q000737:chemistry / Q000378:metabolism*; D025341:Principal Component Analysis; D013260:Steroids, Heterocyclic / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
D060406:Brassinosteroids; D002777:Cholestanols; D011083:Polycyclic Compounds; D013260:Steroids, Heterocyclic; C023623:brassinolide