Synthesis, biological activity and receptor-based 3-D QSAR study of 3 '-N-substituted-3 '-N-debenzoylpaclitaxel analogues

Abstract

3'-N-Substituted-3'-N-debenzoylpaclitaxel analogues were synthesized and investigated for their 3-D QSAR by using comparative molecular field analysis (CoMFA). The CoMFA model obtained from receptor(microtubule)-paclitaxel binding structure displays an excellent predictive power to forecast the biological activity of new 3'-N-substituted-3'-N-debenzoylpaclitaxel analogues as well as the ability to explain the activity of the known paclitaxel analogues. The cross-validated r(cv)(2) values of the CV selected models are 0.835 and 0.616 for A549 and SK-OV-3, respectively, and the non-cross-validated r(ncv)(2) values of them are 0.992 and 0.974. (C) 2002 Elsevier Science Ltd. All rights reserved.