Background:
Thiadiazole has attracted a great deal of interest as a versatile heterocycle for the discovery and development of
potent anticancer agents. Thiadiazole derivatives exert potent antitumor activity against a variety of human cancer cell lines through
various mechanisms.
Objective:
The goal of this work was to design and synthesize thiadiazole-based anticancer agents with anti-angiogenic activity.
Methods:
N-aryl-2-[(5-(aryl)amino-1,3,4-thiadiazol-2-yl)thio]acetamides (4a-r) were synthesized via the reaction of 5-(aryl)amino-1,3,4-
thiadiazole-2(3H)-thiones with N-(aryl)-2-chloroacetamides in the presence of potassium carbonate. The compounds were investigated
for their cytotoxic effects on three cancer (A549, HepG2, SH-SY5Y), two normal (HUVEC and 3T3-L1) cell lines using MTT and WST1 assays. In order to examine whether the compounds have anti-angiogenic effects or not, HUVEC were cultured on matrigel matrix to
create a vascular-like tube formation.
Results:
Compounds 4d, 4m and 4n were more effective on A549 human lung adenocarcinoma cells than cisplatin. The IC50 values of
compounds 4d, 4m and 4n for A549 cell line were found to be 7.82±0.4, 12.5±0.22, 10.1±0.52 µM, respectively when compared with
cisplatin (IC50= 20±0.51 µM), whilst their IC50 values for HUVEC cell line were determined as 138.7±0.84, 78±0.44, 177.6±0.2 µM,
respectively after 48 h treatment. The concentrations (10-20-50 µM) of compounds 4d, 4e, 4l, 4m, 4n, 4q and 4r were found to inhibit
vascular like tube formation.
Conclusion:
According to their anticancer and anti-angiogenic effects, compounds 4d, 4m and 4n may be potential anticancer agents for
further in vivo studies.
Topo II inhibition and DNA intercalation by new phthalazine-based derivatives as potent anticancer agents: design, synthesis, anti-proliferative, docking, and in vivo studies
