Docking, CoMFA and CoMSIA Studies of a Series of N-Benzoylated Phenoxazines and Phenothiazines Derivatives as Antiproliferative Agents

摘要

Using generated conformations from docking analysis by Gold algorithm, some 3D-QSAR models; CoMFA and CoMSIA have been created on 39 N-benzoylated phenoxazines and phenothiazines, including their Soxidized analogues. These molecules inhibit the polymerization of tubulin into microtubules and thus they have been studied for the development of antitumor drugs. Training set for the CoMFA and CoMSIA models using 30 docked conformations gives q2 Leave one out (LOO) values of 0.756 and 0.617, and r2 ncv values of 0.988 and 0.956, respectively. The ability of prediction and robustness of the models were evaluated by test set, cross validation (leave-one-out and leave-ten-out), bootstrapping, and progressive scrambling approaches. The allorientation search (AOS) was used to achieve the best orientation to minimize the effect of initial orientation of the structures. The docking results confirmed CoMFA and CoMSIA contour maps. The docking and 3DQSAR studies were thoroughly interpreted and discussed and confirmed the experimental pIC50 values.