Background: Based on the biological signicance of benzisoselenazolone
and 1,3,4-thiadiazole, a series of novel 1,3,4-thiadiazole derivatives incorporating
benzisoselenazolone scaffold were designed and synthesized with ebselen
as a lead compound.
Methods: Meanwhile, their in vitro antitumor activities were evaluated against
SMMC-7721, MCF-7 and A549 human cancer cell lines by CCK-8 assay.
Results: The preliminary bioassay results demonstrated that all tested compounds
4a-q showed potent antitumor activities, and some compounds exhibited better effects
than positive control ethaselen and 5-fluorouracil (5-FU) against various
cancer cell lines. Furthermore, compounds 4b and 4m showed significant antitumor activities against
SMMC-7721 cells with IC50 values of 1.89 and 1.89 M, respectively. Compounds 4c and 4n displayed
highly effective biological activities against MCF-7 cells with IC50 values of 2.88 and 2.28
M, respectively. Compound 4i showed the best inhibitory effect against A549 cells with IC50 value
of 1.76 M.
Conclusion: The pharmacological results suggest that the substituent groups of phenyl ring on the
1,3,4-thiadiazole are vital for modulating antitumor activities against various cancer cell lines.