Antimalarial activities, QSAR

R. Modeling antimalarial activity application of kinetic energy density quantum similarity measures as descriptors in QSAR./. Chem. Inf. Comput. Sci. 2000, 40, 1400—1407. 

We mentioned earlier the in vitro antimalarial activity of halichondramide and swin-holide A.22 The initial testing of compounds 3 to 5 displayed 75 to 100% mortality of both corn rootworm and tobacco budworm. On titration, they displayed an LCS0 range of 10 to 100 ppm, and induced 30, 85, and 30% corn rootworm larval stunting, respectively. Both halichondramide and swinholide A caused 85% tobacco budworm larval stunting. The significant insecticidal activity of these compounds (3 to 5) indicates that further QSAR studies of the compounds would be valuable. These compounds illustrate the necessity to examine various marine macrolides as potential prototype insecticides. 

Pinheiro, J.C., Kiralj, R. and Ferreira, M.M.C. (2003) Artemisinin derivatives with antimalarial activity against Plasmodium falciparum designed with the aid of quantum chemical and partial least squares methods. QSAR Comb. Sci., 22, 830-842. 

Stiefl, N., Bringmann, G., Rummey, C. and Baumann, K. (2003) Evaluation of extended parameter sets for the 3D-QSAR technique MaP implications for interpretability and model quality exemplified by antimalarially active naphthylisoquinoline alkaloids. /. Comput. Aid. Mol. Des., 17, 347-365. 

In this manner, QSAR models can be derived for very large and heterogeneous data sets (e.g., Eq. (50) for the antimalarial activity of substituted phenanthrenes, quinolines and pyridines) [80] ... 

Modeling Antimalarial Activity Application of Kinetic Energy Density Quantum Similarity Measures as Descriptors in QSAR. 

M. Grigorov, J. Weber, J. M. J. TroncheL C. W. Jefford, W. K. Milhous, and D. Marie, A QSAR study of the antimalarial activity of some synthetic 1,2,4-ttioxanes, Journal of Chemical Irformation and Computer Science, 37, 124, 1997. 

Most QSAR equations will have a contribution from P or from tt or from both. However, there are examples of drugs which have only a slight contribution. For example, a study on antimalarial drugs showed very little relationship between anti-malarial activity and hydrophobic character. This finding lends support to the theory that these drugs are acting in red blood cells, since previous research has shown that the ease with which drugs enter red blood cells is not related to their hydrophobicity. 

Although the presented results do not offer the possibility to predict antimalarial potency in a quantitative manner, this method apparently allows an efficient discrimination between active and inactive analogues. Moreover, it takes into account aspects of charge delocalization which are difficult to capture by means of force-field based methods such as CoMFA. In view of the time and cost involved in such calculations, however, the authors propose this computationally more sophisticated method as a second selection step which could best be used after having sorted out the more active from the less active candidates by a less expensive 3D-QSAR modelling technique [110]. 

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