COMPUTATIONAL STUDIES OF THE STRUCTURES AND PROPERTIES OF POTENTIAL ANTIMALARIAL COMPOUNDS BASED ON THE 1,2,4-TRIOXANE RING STRUCTURE .1. ARTEMISININ-LIKE MOLECULES

Artemisinin and related molecules are potential antimalarials that contain the 1,2,4-trioxane ring system. Several new derivatives have been synthesized and tested in Geneva, and this article presents the results of a systematic study of the structure of these molecules, both by the semiempirical PM3 method and using ab initio SCF methods. The results highlight the feasibility of full optimizations with 3-21G and 6-31G* basis sets for these large molecules. Molecular electrostatic potential (MEP) maps are evaluated and used in an attempt to identify the key features of the molecules that are necessary for their activity. There is good agreement between the PM3 and ab initio maps as to the qualitative predictions. (C) 1994 John Wiley & Sons, Inc.