QSAR Analysis of Camptothecin Analogs as Topoisomerase 1 Inhibitors using Fragmenting Group Based Technology

A database of 413 camptothecin analogs was subjected to fragment-based G-QSAR technology to study the effect of individual rings of camptothecin on the biological activity against Topoisomerase 1 enzyme. Molecules were divided into 2 fragments based on the fragmentation rules. In order to consider the environment of the neighboring fragment(s), the attachment point atoms were also included in the fragments. With the help of the GQSAR technique, 2 models were constructed based on 2 fragments that were generated. By taking the 2 models together a consensus model was prepared. G-QSAR model generated using all classes of camptothecin analogues can be used for the prediction of the biological activity of new compounds. The GQSAR model developed provides optimum ranges for variations for the design of new compounds. The global GQSAR model predicts the activity of compounds better than the previously existing models as it considers the individual fragments of camptothecin. The consensus model gives specific descriptors that are indicative of the activity of the molecules based on individual fragments. This model can be used to develop novel and better camptothecin analogs.