Synthesis and molecular modeling: related approaches to progress in brassinosteroid research

In the field of brassinosteroids, which are potent plant growth regulators, we have developed a quantitative structure-activity relationship study to develop knowledge from a structural point of view and to find out new requirement definitions. This will help identify other suitable active brassinosteroid derivatives with a good activity/synthetic cost ratio for further application in agriculture. The methodology used to achieve this goal represents a multidisciplinary study involving synthesis, molecular modeling calculations, and bioactivity evaluation. The influence of different molecular properties in the bioactivity of a set of synthetic compounds (i.e., molecular electrostatic potential and the ability to form H bonds) is discussed. The molecular electrostatic potential is expressed in terms of the electrostatic Carbó similarity index (CI) between brassinolide (1) and other brassinosteroids. We have found that the electrostatic charges of the functional groups play an important role in the description of the activity, as evidenced by its good correlation with the CI in most cases. Deviation from this rule could be explained by the H bonding abilities of some of these compounds, which we believe may play an essential role in binding to the natural receptors.