QSAR study for cytotoxicity of diterpenoid tanshinones.

A quantitative structure-activity relationship (QSAR) of a series of tanshinone compounds with cytotoxicity against murine leukemia cell lines P-388 has been studied using density functional theory (DFT) method combined with statistical analysis. Four main independent factors contributing to the cytotoxicity including the maximum molecular electrostatic potential at the SAS surface (SAS (max)), the average nucleophilic superdelocalizability (ANS), the dihedral between ring A and B (u) and the net atomic charge of C (12) (Q(C (12))) were selected by stepwise multiple regression method, then the QSAR equation was established via multiple linear regression (MLR) analysis. These descriptors accounted for 74.2% of the variation in the in vitro biological activity among the tanshinone analogues. The QSAR equation was used to estimate the cytotoxicity for new compounds of this series by calculating the four descriptors. Based on this model, six new compounds with higher cytotoxicity were theoretically designed.