Background: For decades, a great deal of research work has been done to synthesize ellipticine and
its derivatives because of their potential antitumor properties and anti-HIV activities. However, the resonance
structures in different media, a low level of solubility at physiological pH and systemic toxicity have prevented
the use of ellipticine as a therapeutic agent. Besides, the low yield and complex steps of ellipticine synthesis limit
Methods: A high-yield synthetic procedure of ellipticine has been optimized, and the total yield was up to 50%
without silica gel column chromatography. Novel hexacyclic ellipticine derivatives were synthesized by coupling
ellipticine with o-aminobenzoic acid. Their cytotoxicities against HCT116, MGC803, HT29 and MCF-7 tumor
cells were evaluated.
Results: The synthesis process of ellipticine was optimized, and the total yield of the synthetic route was increased
to 50% through several operation steps optimization. Fourteen ellipticine hexacyclic derivatives were
synthesized. The synthetic compounds were screened for anti-tumor activity in vivo and in vitro, and some of the
derivatives had good anti-tumor activity.
Conclusion: Compared with ellipticine, the compound 1l showed higher antitumor activity and better tolerance to
tumor models. The compound 1l treatment increased the percentage of late apoptotic cells from 3.1% (DMSO) to
21.6% (20.0 μM) in NCI-H460 cells. It also was observed the effect of 1l on G2 phase arrest was similar as that
of ellipticine. The mechanism of action indicated compound 1l could be a topoisomerase IIα poison. These studies
provided the basis for the pharmacodynamics and toxicology of ellipticine, and further clarifies the structureactivity
relationship of antitumor activity of ellipticine.