Several (+)-goniofufurone analogues with simplified structures were designed,
synthesized and evaluated for their in vitro antitumour activity against a
panel of human tumour cell lines. Dephenylated compounds 2 and 3,
demonstrated remarkable antitumour activities, in the cultures of K562 and
Raji cells with IC50 values in the range of 3.0-9.3 nM. Each of
goniofufurone analogues lacking the tetrahydrofuran ring (4, 5 and 6)
strongly inhibited the growth of at least one malignant cell line, with IC50
values in the range of 11-30 nM. Brief SAR analysis showed that the
simplified goniofufurone analogues, designed by removing the phenyl group
from C-7, or by opening the THF ring, could show stronger antiproliferative
effects compared to control molecules. It is noticeable that analogues 2-8
are completely inactive with respect to the normal MRC-5 cell line. These
findings, together with their potent antitumor activities, provide a
suitable basis for the development of new and selective antitumour drugs.