Preclinical And Phase Ⅰ Clinical Trials Of Salvicine

Salvicine (SAL) was the novel diterpenoid quinone compound synthesized by the structural modification of a natural product lead isolated from a Chinese medicinal plant, Salvia prionitis lance (Labiatae). It displayed potent in vitro and in vivo anticancer activities with relative selectivity. SAL was a novel non-DNA-intercalative topoisomerase â…¡ (Topo â…¡) inhibitor. It acted on the multi-steps of the catalytic cycle of Topo â…¡, including promoting Topo â…¡ -DNA binding and inhibiting pre-and post-strand-mediated DNA religation without interference with the forward cleavage steps, which indicated that SAL could result in DNA breaks through trapping "cleavable complex" consisting of Topo â…¡ and DNA.The purposes of this study were: firstly, to demonstrate preclinical antitumor ability of SAL in vitro by cell toxicity, cell DNA damage and cell apoptosis experimentation , then to evaluate the safety and maximum tolerated dose (MTD) of SAL in patients with malignant tumors, and to investigate pharmacokinetics parameters of SAL. At same time, the second purposes were to study the antitumor effects of SAL in patients with malignant tumors.As a control, Etopotide (VP-16) was used in the present study, and we conformed the antitumor ability of SAL in vitro by cell toxicity, cell...