One-Pot Synthesis of Novel Thiazoles as Potential Anti-Cancer Agents
| Autor: | Mahgoub M Ahmed, Sobhi M. Gomha, Hatem M. Gaber, Zeinab A. Muhammad, Eman A. Taher, Hesham R. El-Seedi, Abdelwahed R. Sayed |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pharmacology Cisplatin Pharmaceutical Science 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Harmine chemistry Mechanism of action Apoptosis 030220 oncology & carcinogenesis Drug Discovery medicine medicine.symptom Growth inhibition Thiazole IC50 Semicarbazone medicine.drug Nuclear chemistry |
| Zdroj: | Drug Design, Development and Therapy. 14:1363-1375 |
| ISSN: | 1177-8881 |
| DOI: | 10.2147/dddt.s221263 |
| Popis: | 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, 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. |
| Databáze: | OpenAIRE |
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