Lindera megaphylla has been traditionally used as
an antineoplastic and wound healing remedy.We
previously demonstrated the antitumor effects of
D-dicentrine, a natural aporphine alkaloid from
the root of L. megaphylla. To generate analogues,
series of phenanthrene alkaloids from D-dicentrine
were synthesized by degradation with ethyl
chloroformate in pyridine, base hydrolysis, and Nalkylation.
In this study, we demonstrated that
one of the synthesized D-dicentrine analogues
(here after designated as analogue 1) exhibited
more potent cytotoxic effects than D-dicentrine
in colon adenocarcinoma, hepatoma, leukemia,
and epidermoid carcinoma cells. We performed
cell cycle and apoptotic analysis by flow cytometry,
an apoptotic DNA detection ELISA assay, and
topoisomerase II activity by the kinetoplast DNA
concatenation assay for studying their cytotoxic
mechanisms. We found that both D-dicentrine
and analogue 1 induced apoptosis and G2/M arrest
histonebound
DNA fragments. Moreover, we found thatanalogue 1 was 28-fold more potent than D-dicentrinefor inhibition of topoisomerase II activityby the kinetoplast DNA concatenation assay. Ourfindings indicate that D-dicentrine analogue 1 isvery promising as a potential antitumor agent forfuture study.apoptotic cells induced by analogue 1 was 4.5-fold higher than that induced by D-dicentrine asevident from measuring the amount of histoneboundhistoneboundDNA fragments. Moreover, we found thatanalogue 1 was 28-fold more potent than D-dicentrinefor inhibition of topoisomerase II activityby the kinetoplast DNA concatenation assay. Ourfindings indicate that D-dicentrine analogue 1 isvery promising as a potential antitumor agent for
