Conclusion: activity against cancer cell line PC3-MM2 of the novobiocin compounds closely correlated with 3 structural parameters being screened using classical statistical methods including ALogP2, minHBint7 and Weta1, mass, Combining with ANN simulation shows 3 - 2 - 1 nonlinear model explained 88% of the structural elements which have an important role in determining antitumor activity of these compounds.