Drug design, molecular modelling, and QSAR studies of antimalarial mefloquine and artemisinin derivatives

Suman Sirimulla, University of Texas at El Paso


A common procedure for QSAR analysis consist of data selection (generally sets of homologous series of compounds and their corresponding biological activities), tabulation of trial physicochemical or molecular structural descriptors, followed by a multilinear statistical analysis to derive a statistically valid QSAR correlation of the activity data making use of a subset of the trial descriptors. A final important step is cross-validation to assess the putative predictive (rather than just correlative) capabilities of the derived QSAR model equation. This thesis consists of QSAR model development studies for two data sets. The results presented in this first study will consist of an analysis and criticism of a research paper in which antimalarial activities of a set of aromatic mefloquine derivatives are correlated with calculated atomic charges, using increasingly complex statistical procedures. However, the structures used in the analysis did not actually correspond to the experimental structures. The results of a very successful elementary QSAR study using substituent indicator variables, coupled with two calculated theoretical AM1 parameters for the actual compounds used in the work outlined above are presented.^ The second QSAR analysis consists of a study of a 74 compound data set of antimalarial artemisinin derivatives. The analysis protocol employs hierarchical molecular structural descriptors, which are correlated with biological activities using multilinear regression analysis. The levels of hierarchical structural descriptors are augmented and tested sequentially to obtain information regarding the lowest levels of descriptors that are crucial for statistically significant rectification of a particular dependent variable property. These concepts are illustrated with biological data comprised of antimalarial activities of Artemisinin derivatives with a wide variety of substituents groups. The first few levels of hierarchical descriptors derived from the molecular structure. The final level consists of quantum mechanical descriptors derived from AM1 calculations using SPARTAN software. The equation defined by the above QSAR procedure may be used to correlate the antimalarial activities of similar type of compounds.^

Subject Area

Health Sciences, Pharmacology|Chemistry, Pharmaceutical

Recommended Citation

Sirimulla, Suman, "Drug design, molecular modelling, and QSAR studies of antimalarial mefloquine and artemisinin derivatives" (2007). ETD Collection for University of Texas, El Paso. AAI1454188.