Aconitum and Delphinium alkaloids: “Drug-likeness” descriptors related to toxic mode of action

Large series of Aconitum and Delphinium alkaloids have been investigated by means of QSAR analysis. Descriptors related to “drug-likeness” of molecules were selected to discriminate between “drugs” and “non-drugs” amongst diterpenoid alkaloids of interest. A usefulness of such approach has been assessed and it proved to give reliable results on whether a particular diterpenoid alkaloid is likely to be either poison or drug. A number of QSAR models with “drug-likeness” descriptors have also been obtained and discussed in terms of their relativity to the mode of toxic action exhibited by the alkaloids. The QSAR models were obtained with r value in the range 0.69–0.94. The q2 (cross validation of r2) values also confirm the statistical significance of our models.