Design, Synthesis and Bio-evaluations of Tetrahydroisoquinolines as Novel Kinesin Spindle Protein (KSP) Inhibitors

摘要

Based on the pharmacophore we have mapped and the binding structure of monastrol with the target protein, a series of tetrahydroisoquinolines have been identified as novel kinesin spindle protein (KSP) inhibitors. Human KSP protein was cloned, expressed and purified; KSP inhibitory activities of the designed compounds were tested. All the designed compounds displayed more potent inhibitory activities in the KSP ATPase assays and about half of them showed better in vitro cytotoxicities against HepG2 cell line, the first reported small molecule KSP inhibitor monastrol was used as a control compound.