Synthesis and Characterization of Some New Bis-Pyrazolyl-Thiazoles Incorporating the Thiophene Moiety as Potent Anti-Tumor Agents
Abstract
:1. Introduction
2. Results
2.1. Synthesis
2.2. Anti-Cancer Activity
- The in vitro inhibitory activities of tested compounds against the human liver carcinoma (HepG2) have the descending order as follow: 3g > 5e > 3e > 10 > 5f > 3i > 3f > 3a > 1 > 3a > 3h > 8 > 5b > 3c > 3b > 3d.
- The thiazole derivatives 5a,b,e,f have in vitro inhibitory activity greater than the bis-thiazole derivatives 3a,b,e,f (5a > 3a, 5b > 3b, 5e > 3e, and 5f > 3f).
- The substituent at position 4 in the thiazole ring affect the in vitro inhibitory activity, while the thienyl ring has a greater effect than the methyl group, which has a greater effect than the phenyl group.
- The introduction of electron-withdrawing group (nitro group > chlorine atom > bromine atom) at the fourth position of the phenyl group at position 5 in the thiazole ring enhances the antitumor activity. In contrast, the introduction of electron-donating group (methoxy group > methyl group) decreases the antitumor activity.
3. Materials and Methods
3.1. General Experimental Procedures
3.2. Synthetic Procedures (See Supplementary Material Figures S1–S16)
3.2.1. General Method for the Synthsis of 1,4-Bis(1-(4-substituted-5-((E)-aryldiazenyl)thiazol-2-yl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-5-yl)benzene 3a–i
3.2.2. Synthesis of 4-Methyl-5-((E)-aryldiazenyl)-2-(2-(1-(thiophen-2-yl)ethylidene)hydrazinyl) Thiazole Derivatives 5a,b,e,f
3.2.3. Alternate Synthesis of Compounds 3a,b,e,f
3.2.4. Synthesis of 2,2′-(5,5′-(1,4-phenylene)bis(3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-3,1-diyl))bis(thiazol-4(5H)-one) (8)
3.2.5. Synthesis of (2Z,2′Z)-dimethyl 2,2′-(2,2′-(5,5′-(1,4-phenylene)bis(5-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-3,1-diyl))bis(4-oxothiazole-2(4H)-yl-5(4H)-ylidene))diacetate (10)
3.2.6. Alternate Synthesis of Compound 10
3.3. Anti-Tumor Activity
4. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Compound No. | R | Ar | IC50 (μM) |
---|---|---|---|
1 | - | - | 4.05 ± 0.17 |
3a | Me | C6H5 | 6.29 ± 0.22 |
3b | Me | 4-MeC6H4 | 18.2 ± 0.14 |
3c | Me | 3-MeC6H4 | 17.6 ± 0.09 |
3d | Me | 4-MeOC6H4 | 52.4 ± 0.17 |
3e | Me | 4-ClC6H4 | 1.62 ± 0.20 |
3f | Me | 4-BrC6H4 | 2.09 ± 0.19 |
3g | Me | 4-NO2C6H4 | 1.37 ± 0.15 |
3h | C6H5 | C6H5 | 10.49 ± 0.22 |
3i | C4H4S | C6H5 | 2.03 ± 0.25 |
5a | Me | C6H5 | 5.13 ± 0.09 |
5b | Me | 4-MeC6H4 | 14.29 ± 0.22 |
5e | Me | 4-ClC6H4 | 1.41 ± 0.17 |
5f | Me | 4-BrC6H4 | 1.93 ± 0.08 |
8 | - | - | 12.37 ± 0.14 |
10 | - | - | 1.86 ± 0.20 |
Doxorubicin | - | - | 0.72 ± 0.18 |
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Gomha, S.M.; Edrees, M.M.; Altalbawy, F.M.A. Synthesis and Characterization of Some New Bis-Pyrazolyl-Thiazoles Incorporating the Thiophene Moiety as Potent Anti-Tumor Agents. Int. J. Mol. Sci. 2016, 17, 1499. https://doi.org/10.3390/ijms17091499
Gomha SM, Edrees MM, Altalbawy FMA. Synthesis and Characterization of Some New Bis-Pyrazolyl-Thiazoles Incorporating the Thiophene Moiety as Potent Anti-Tumor Agents. International Journal of Molecular Sciences. 2016; 17(9):1499. https://doi.org/10.3390/ijms17091499
Chicago/Turabian StyleGomha, Sobhi M., Mastoura M. Edrees, and Farag M. A. Altalbawy. 2016. "Synthesis and Characterization of Some New Bis-Pyrazolyl-Thiazoles Incorporating the Thiophene Moiety as Potent Anti-Tumor Agents" International Journal of Molecular Sciences 17, no. 9: 1499. https://doi.org/10.3390/ijms17091499