[Special Issue for Honor Award dedicating to Prof Kimito Funatsu]An Electronic-Structure Informatics Study on Inhibitory Activity of Natural Products against Fatty Acid Synthase

Abstract

Fatty acid synthase (FASN) inhibitors are known to work as anti-cancer drugs. In order to find important factors in their structure-activity relationships and to derive a predictive model for the activity, we herein tried to develop regression models by using descriptors representing chemical reactivities and intermolecular interactions. By employing the descriptors calculated with the electronic-structure theory, regression models for the experimental IC50 values were derived. Good correlations between the predicted and experimental values were obtained for the natural products having inhibitor activity to FASN. The obtained models are expected useful for systematic search for more efficient inhibitors. At the same time, the present results justify the use of the newly suggested descriptors evaluated in electronic-structure calculations.