Antimalarial activity of dihydroartemisinin derivatives against P-falciparum resistant to mefloquine: a quantum chemical and multivariate study

Dihydroartemisinin derivatives with antimalarial activity against P. falcip arum resistant to mefloquine are proposed with the aid of quantum chemistry and multivariate analysis methods (PCA, KNN, and SIMCA). The principal com ponent analysis (PCA) and hierarchical cluster analysis (HCA) showed that t he descriptors: molecular softness (MS), total surface area (TSA), Randic's index, path-1 molecular connectivity-average (CHl1A), bond information ind ex (BIC), shape index based on paths of length 2 of Kier (2K), and directio nal (related to molecular size, dimension: axis I and weight: van der Waals ' volume) and non-directional (related to linear contribution to the total molecular size and weight: van der Waals' volume) WHIM-31) indices (L1v and Tv), respectively, are responsible for the classification between the high er and lower antimalarial. activity of the derivatives. The compounds predi cted as of high activity by the three methods are 22 and 28 in Fig. 2. (C) 2001 Published by Elsevier Science B.V.