STRUCTURE-PROPERTY CORRELATIONS OF A SERIES OF ANTIMALARIAL CHLOROQUINE DERIVATIVES

As part of the development of our in-house molecular modelling package , COSMIC, the structure-property relationships of a series of 13 antim alarial chloroquine derivatives have been investigated using physicoch emical properties calculated from molecular models. This has involved the use of various statistical techniques. The compounds were analysed using three different modelling approximations concerning assumptions about the invariant amino alkyl side chain. The first two sets of dat a were obtained from models with and without the side shain using a fo rmal charge of 0.0. Analysis of these data using principal components resulted in plots of principal component scores in which activity cate gories were separated. In the third data set, the side chain was model led with a charge of +1 and an examination of the molecular properties showed poorer clustering of activity categories. We have also investi gated relationships between biological activity and physicochemical pr operties using multiple linear regression. Although significant equati ons were developed, the correlation coefficients were low and it was n ot felt that they would be useful for quantitative prediction. The ide ntification of important variables, however, may give some clues to th e mechanism of action of these compounds.