TQ-B3203, a potent proliferation inhibitor derived from camptothecin

To develop topoisomerase I targeted drug candidates with sophisticated liposolubility, a series of novel camptothecin derivatives were synthesized through structure-based molecular hybridization and prodrug design approach. The compounds were used as compositions in micellar emulsion preparations, and the antiproliferative efficacy of these preparations were evaluated in two cancer cell lines (A2780s and A549) in vitro. The designed molecules were afterwards optimized for better potency by modifications at the aliphatic chain, the linker and the camptothecin-yl group to reach the optimal structure 7c (TQ-B3203), an SN-38 (camptothecin derivative, 7-ethyl-camptothecin-10-yl) containing compound. 7c showed excellent capacity of inhibiting cell proliferation with IC 50 value at nanomolar level, and the potency was further confirmed in other human cancer cell lines (HT-29 and HePG2) superior to the positive reference irinotecan. 7c can be a promising candidate as antitumor drug. Its micellar emulsion preparation has succeeded in the preclinical studies and is in process for investigational new drug(IND) application.