Background: Norcantharimides are known as norcantharidine derivatives and contain
an isoindole skeleton structure. Isoindole derivatives have positive effect on inflammatory pathologies
Objective: Considering this information, firstly, isoindole derivatives containing different functional
groups 4-13 have been synthesized from 2-alkyl/aryl-3a, 4,7,7a-tetrahydro-1H-isoindole-1,
Methods: For the synthesis of all compounds, 2-alkyl/aryl-3a, 4,7,7a-tetrahydro-1H-isoindole-
1,3(2H)-dione was used as the starting compound. The syntheses were based on two main reactions:
Ene-reaction of singlet oxygen and epoxidation. Secondly, their anticancer activities were
evaluated against HeLa, C6 and A549 cancer cell lines by the BrdU assay.
Results: Anticancer activities of synthesized compounds (4-13) and 5-FU (5-Florouracil) against
HeLa, C6 and A549 cells were investigated at four concentrations (100, 50, 25 and 5 μM). IC50
values of compounds 4-13 were calculated for all cancer cell lines. The investigated compounds
showed anticancer activity against the cancer cell lines depending on doses. Compound 7 containing
azide and silyl ether exhibited higher inhibitory activity than the other compounds and 5-FU
against A549 cancer cell lines (IC50 =19.41± 0.01 μM). Compounds 9 and 11 were determined to
exhibit cell-selective activity against HeLa cancer cell lines. Compound 11 had higher activity than
the positive control at 100 μM concentrations against C6 cancer cell lines.
Conclusion: According to the results observed, isoindole derivatives 7, 9, and 11 might be good
potential anticancer agents for the treatment of cervical and glioma cancer due to their antiproliferative
properties, having less cytotoxic effects on healthy cells. In addition, compound 7 could be
used in in vivo studies of all three-cancer cell lines (C6, HeLa, and A549).