Quantitative structure–activity relationships of xanthen-3-one and xanthen-1,8-dione derivatives and design of new compounds with enhanced antiproliferative activity on HeLa cervical cancer cells

Abstract

Xanthene derivatives have become a group of molecules of great importance in discovering of new anticancer drugs. Recent studies of our group performed on xanthen-3-one and xanthen-1,8-dione derivatives have shown their antiproliferative activity on HeLa cervical cell lines. Obtained IC50 values together with calculated molecular descriptors were subjected to Quantitative Structure–Activity Relationship (QSAR) study in order to identify the most relevant molecular features responsible for the observed antiproliferative activity of compounds. Partial least square statistical method and the same training and test set were used to obtain statistical parameters for internal and external validation in 2D- and 3D-QSAR study. The obtained QSAR models have shown next results: 2D-QSAR: R 2 = 0.741, Q 2 = 0.792, R 2 pred = 0.875 and 3D-QSAR: R 2 = 0.951, Q 2 = 0.830, R 2 pred = 0.769. Based on the performed QSAR analysis and calculated ADMET properties, novel xanthene derivatives with enhanced antiproliferative activity were designed. Communicated by Ramaswamy H. Sarma