Theoretical Studies for Molecular Modeling of New Camptothecin Analogues

Irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino carbonyloxycamptothecin: CPT-11) is a widely used potent antitumor drug that is developed based on camptothecin. However, overexpression of ABCG2 (BCRP/MXR/ABCP) confers cancer cells resistance to SN-38, that is, the active metabolite of irinotecan. In the present study to develop a platform for the molecular modeling to circumvent cancer drug resistance associated with ABCG2, we have characterized a total of fourteen new SN-38 analogues by some typical properties, which were evaluated by molecular orbital (MO) calculations and neural network (NN) QSAR technique