Subhendu Chakroborty - Pharmacophore Modeling of Substituted 1,2,4-Trioxanes for Quantitative Prediction of their Antimalarial Activity

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      Publication Details (including relevant citation   information):

      J. Chem. Inf. Model., Article ASAP
      DOI: 10.1021/ci100180e
      Publication Date (Web): July 27, 2010

      Abstract:

      A pharmacophore model has been developed for determining the   essential  structural requirements for antimalarial activity   from the eight series  of substituted 1,2,4-trioxanes. The   best pharmacophore model possessing  two aliphatic   hydrophobic, one aromatic hydrophobic, one hydrogen-bond    (H-bond) acceptor, and one H-bond acceptor (lipid) feature   for  antimalarial activity showed an excellent correlation   coefficient for  the training   (r2training = 0.85) and a fair   correlation coefficient for the test set   (r2test = 0.51) molecules. The   model predicts well to other known substituted    1,2,4-trioxanes including those which either are drugs or are   undergoing  clinical trials. In order to further validate   this model, five  substituted 1,2,4-trioxanes were   synthesized from the generated focused  library and screened   for antimalarial activity. The observed activity of  these   molecules was consistent with the pharmacophore model,   suggesting  that the model may be useful in the design of   potent antimalarial  agents.

      Address (URL): http://pubs.acs.org/doi/abs/10.1021/ci100180e