Discodermolide, which acts on tubulin, is a novel and anti-tumor compound. It has good pharmaceutical prospect. For purpose of designing more potent analogues, three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were carried out on discodermolide and its derivatives using comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). The best predictions were obtained with the CoMFA steric, electrostatic fields (leave-one-out q2＝0.592, no validation r2＝0.982, standard error of estimate＝0.094, F＝119.761), and with the CoMSIA combined electrostatic, hydrophobic, H-bond donor and acceptor fields (leave-one-out q2＝0.544, no validation r2＝0.980, standard error of estimate＝0.098, F＝108.715). Our results show that the obtained CoMFA and CoMSIA models have good predict ability, which can be used for designing of homologic compounds.

Key words: discodermolide, 3D-QSAR, tubulin