Structure Activity Relationship and Quantitative Structure-Activity Relationships Modeling of Antitrypanosomal Activities of Alkyldiamine Cryptolepine Derivatives

QSAR studies have been performed on twenty-two molecules of alkyldiamine cryptolepine derivatives. The compounds used are potent inhibitors of the trypanosome papain-like cysteine proteases, which could, at least in part, explain their antitrypanosomal activity. Qualitative approximations of the structure activity relationships were applied to this series of twenty-two compounds to determine the role of several physicochemical properties which are used in QSAR modeling as independent variables. A multiple linear regression (MLR) procedure was used to envisage the relationships between molecular descriptors and the activity of alkyldiamine cryptolepine derivatives. The predictivity of models was estimated by cross-validation with the leave-one-out method. Our results suggest QSAR models based of the following descriptors: SAG, V, HE, log P and MW for the inhibitory activities of cysteine proteases from trypanosoma cruzain and trypanosoma rhodesain. Results show high correlation between experimental and predicted activity values, indicating the validation and the good quality of the derived QSAR models.