One-Pot Synthesis of Novel Thiazoles as Potential Anti-Cancer Agents.

BACKGROUND

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSION

Thiazole scaffolds and showed anticancer activities in the micromolar range and are appropriate as a candidate for cancer treatment.