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Abdelwahed R Sayed,1,2 Sobhi M Gomha,3,4 Eman A Taher,5,6 Zeinab A Muhammad,5 Hesham R El-Seedi,6,7 Hatem M Gaber,5 Mahgoub M Ahmed8 1Department of Chemistry, Faculty of Science, KFU, Hofuf, Saudi Arabia; 2Department of Chemistry, Faculty of Science, Beni-suef University, Beni-suef, Egypt; 3Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt; 4Department of Chemistry, Faculty of Science, Islamic University in Almadinah Almonawara, Almadinah Almonawara 42351, Saudi Arabia; 5Department of Pharmaceutical Chemistry, National Organization for Drug Control and Research (NODCAR), Giza 12311, Egypt; 6Chemistry Department, Faculty of Science, El-Menoufia University, Shebin El-Kom 32512, Egypt; 7Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Uppsala SE-75123, Sweden; 8Molecular Drug Evaluation Department, National Organization for Drug Control and Research (NODCAR), Giza 12311, EgyptCorrespondence: Sobhi M Gomha Tel +20 100-164-9576Fax +20 25685799Email s.m.gomha@gmail.comBackground: 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, 1H-NMR and 13C-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 μM, respectively, compared to harmine (IC50 = 2.40 ± 0.12 μM) and cisplatin (IC50 = 5.18 ± 0.94 μM) reference drugs. Also, compounds 8c, 4d and 4c showed promising IC50 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 (IC50 = 4.59 ± 0.67 μM) and cisplatin (IC50 = 11.68 ± 1.54 μM). On the other hand, compounds 4d, 4c, 8c and 11c were the most active (IC50 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 (IC50 = 2.54 ± 0.82 μM) and cisplatin (IC50 = 41 ± 0.63 μM). 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.Keywords: hydrazones, hydrazonoyl halides, cyclization, harmine, HCT-116, HepG2, HT-29 |
