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-1-NMR and C-13-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 4c, 4d and 8c showed growth inhibition activity against HCT-116 with IC50 values of 3.80 +/- 0.80, 3.65 +/- 0.90 and 3.16 +/- 0.90 mu M, respectively, compared to harmine (IC50 = 2.40 +/- 0.12 mu M) and cisplatin (IC50 = 5.18 +/- 0.94 mu M) reference drugs. Also, compounds 8c, 4d and 4c showed promising IC(50 )values of 3.47 +/- 0.79, 4.13 +/- 0.51 and 7.24 +/- 0.62 mu M, respectively, against the more resistant human colorectal cancer (HT-29) cell line compared with harmine (IC50 = 4.59 +/- 0.67 mu M) and cisplatin (IC50 = 11.68 +/- 1.54 mu M). On the other hand, compounds 4d, 4c, 8c and llc were the most active (IC50 values of 2.31 +/- 0.43, 2.94 +/- 0.62, 4.57 +/- 0.85 and 9.86 +/- 0.78 mu M, respectively) against the hepatocellular carcinoma (HepG2) cell line compared with harmine (IC50 = 2.54 +/- 0.82 mu M) and cisplatin (IC50 = 41 +/- 0.63 pM). The study also suggested that the mechanism of the anticancer action exerted by the most active compounds (4c, 4d and 8c) inside HCT-116 cells was apoptosis through the Bcl-2 family. Conclusion: Thiazole scaffolds 4c, 4d and 8c showed anticancer activities in the micromolar range and are appropriate as a candidate for cancer treatment.