ABSTRACT
Ten novel compounds, each consisting of two subunits and a linker, were designed with the aid of molecular modeling to resemble the natural steroidal phytohormone brassinolide. The mimetics were synthesized and subjected to the rice leaf lamina inclination bioassay to test for brassinosteroid activity. Most of the mimetics displayed very weak or no bioactivity, but two were strongly active when coapplied with the auxin indole-3-acetic acid (IAA), which synergizes the activity of brassinosteroids. Thus, 1-(4,6 alpha,7 alpha-trihydroxy-5,6,7,8-tetrahydronaphthyl)-2-(6 alpha',7 alpha'-dihydroxy-5',6',7',8'-tetrahydronaphthyl)ethyne (4) and (E)-1,2-bis[trans-(4a alpha,8a beta)-4-oxo-6 alpha,7 alpha-dihydroxy-4a,5,6,7,8,8a-hexahydro-(3H)-naphthyl]ethylene (11) showed exceptional activity at doses as low as 0.01 ng and 0.001 ng/plant, respectively. These compounds are the first biologically active nonsteroidal brassinolide mimetics.
Subject(s)
Cholestanols/chemical synthesis , Plant Growth Regulators/chemical synthesis , Plant Growth Regulators/pharmacology , Steroids, Heterocyclic/chemical synthesis , Brassinosteroids , Cholestanols/chemistry , Cholestanols/pharmacology , Dose-Response Relationship, Drug , Drug Design , Drug Synergism , Indoleacetic Acids/pharmacology , Models, Molecular , Molecular Mimicry , Molecular Structure , Oryza/drug effects , Plant Growth Regulators/chemistry , Plant Leaves/drug effects , Steroids, Heterocyclic/chemistry , Steroids, Heterocyclic/pharmacology , Structure-Activity RelationshipABSTRACT
The reduction of castasterone with sodium in ethanol produced chiefly the known 6alpha-hydroxy stereoisomer, whereas reduction with sodium orohydride in methanol afforded mainly the novel 6beta-epimer. Both compounds showed variable bioactivity through four separate assays via the rice leaf lamina inclination bioassay. However, when treated with an appropriate statistical program to remove outliers, the averaged results clearly indicated that the two 6-hydroxy epimers possess comparable and significant bioactivity, which is, however, lower than that of castasterone or brassinolide. When applied together with 1000 ng of the auxin, indole-3-acetic acid (IAA), the activity of both the 6alpha and 6beta hydroxy epimers was enhanced by ca. one order of magnitude across a wide range of doses.
