Abstract
Thiazole and thiosemicarbazone derivatives are known to have potential anticancer activity with a mechanism of action related to inhibition of matrix metallo-proteinases, kinases and anti-apoptotic BCL2 family proteins.
A novel three series of 5-(1-(2-(thiazol-2-yl)hydrazono)ethyl)thiazole derivatives were prepared in a one-pot three-component reaction using 2-(2-benzylidene hydrazinyl)-4-methylthiazole as a starting precursor. MS, IR,
H-NMR and
C-NMR were used to elucidate the structures of the synthesized compounds. Most of the synthesized products were evaluated for their in vitro anticancer screening against HCT-116, HT-29 and HepG2 using the MTT colorimetric assay.
The results indicated that compounds
and
showed growth inhibition activity against HCT-116 with IC
values of 3.80 ± 0.80, 3.65 ± 0.90 and 3.16 ± 0.90 μM, respectively, compared to harmine (IC
= 2.40 ± 0.12 μM) and cisplatin (IC
= 5.18 ± 0.94 μM) reference drugs. Also, compounds
and
showed promising IC
values of 3.47 ± 0.79, 4.13 ± 0.51 and 7.24 ± 0.62 μM, respectively, against the more resistant human colorectal cancer (HT-29) cell line compared with harmine (IC
= 4.59 ± 0.67 μM) and cisplatin (IC
= 11.68 ± 1.54 μM). On the other hand, compounds
and
were the most active (IC
values of 2.31± 0.43, 2.94 ± 0.62, 4.57 ± 0.85 and 9.86 ± 0.78 μM, respectively) against the hepatocellular carcinoma (HepG2) cell line compared with harmine (IC
= 2.54 ± 0.82 μM) and cisplatin (IC
= 41 ± 0.63 μM). The study also suggested that the mechanism of the anticancer action exerted by the most active compounds (
and
) inside HCT-116 cells was apoptosis through the Bcl-2 family.
Thiazole scaffolds
and
showed anticancer activities in the micromolar range and are appropriate as a candidate for cancer treatment.