The cytotoxic activity of
camptothecin derivatives is so high that these compounds need to be further modified before their successful application as anti-
cancer agents clinically. In this study, we reported the synthesis and biological evaluation of a novel
camptothecin derivative called compound 2-47. The changes in structure did not reduce its activity to inhibit
DNA topoisomerase I. Compound 2-47 induced apoptosis of many
tumor cells including
leukemia cells K562, Jurkat, HL-60,
breast cancer cell BT-549,
colon cancer cell HT-29 and
liver cancer cell HepG2 with a half maximal inhibitory concentration (IC50) of 2- to 3-fold lower than
HCPT as a control. In particular, 2-47 inhibited the proliferation of Jurkat cells with an IC50 of as low as 40 nM. By making use of Jurkat cell as a model, following treatment of Jurkat cells, compound 2-47 activated
caspase-3 and PARP, resulting in a decreased Bcl-2/Bax ratio. These data showed that compound 2-47 induces Jurkat cell death through the mitochondrial apoptotic pathway. In addition, compound 2-47 showed a decreased cytotoxic activity against normal cells and an improved solubility in low-polar
solvent. For example, compound 2-47 solutes in CHCl3 130-fold higher than
HCPT. Taken together, our data demonstrated that
camptothecin derivative 2-47 notably inhibits the
tumor cell proliferation through mitochondrial-mediated apoptosis in vitro.