Synthesis and Biological Evaluation of Novel Benzothiazole-2-thiol Derivatives as Potential Anticancer Agents
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Biological Activities
Compd. | R1 | R2 | IC50 (µM) a | ||
---|---|---|---|---|---|
HepG2 | SW480 | HeLa | |||
1 | 4-chlorobenzyl | 2-methoxyphenyl | 0.7 | 5.6 | 4.0 |
2 | benzyl | chloromethyl | 1.0 | 5.2 | 4.6 |
7a | benzyl | chloroethyl | 5.6 | 15.7 | 8.6 |
7b | benzyl | bromoethyl | 6.6 | 14.9 | 48.1 |
7c | 2-pyridinyl | chloromethyl | 0.7 | 2.3 | 3.1 |
7d | 5-chloro-2-pyridinyl | chloromethyl | 0.26 | 0.46 | 0.035 |
7e | 5-bromo-2-pyridinyl | chloromethyl | 0.048 | 0.68 | 0.02 |
7f | 5-methyl-2-pyridinyl | chloromethyl | 0.091 | 1.0 | 0.03 |
7g | 3-pyridinyl | chloromethyl | 6.6 | 6.4 | 12.6 |
7h | 2-chloro-4-pyridinyl | chloromethyl | 5.0 | 2.9 | 1.9 |
7i | 2-chloro-4-methyl-3-pyridinyl | chloromethyl | 0.4 | 2.4 | 0.4 |
7j | 2-pyrimidinyl | chloromethyl | 24.3 | 54.8 | 24.3 |
7k | 2-thiazolyl | chloromethyl | 13.1 | 7.1 | 14.5 |
7l | 2-pyridinyl | 2-methoxyphenyl | >100 | >100 | >100 |
7m | 5-chloro-2-pyridinyl | 2-methoxyphenyl | >100 | >100 | 0.6 |
7n | 5-bromo-2-pyridinyl | 2-methoxyphenyl | 23.5 | 23.8 | 23.5 |
7o | 5-methyl-2-pyridinyl | 2-methoxyphenyl | 45.6 | 31.1 | 0.8 |
7p | 3-pyridinyl | 2-methoxyphenyl | >100 | >100 | >100 |
7q | 2-chloro-4-pyridinyl | 2-methoxyphenyl | >100 | >100 | >100 |
7r | 2-chloro-4-methyl-3-pyridinyl | 2-methoxyphenyl | 23.1 | >100 | 34.6 |
7s | 2-pyrimidyl | 2-methoxyphenyl | 27.2 | >100 | >100 |
7t | 2-thiazolyl | 2-methoxyphenyl | >100 | >100 | >100 |
Compd. | IC50(µM) a | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
HCT116 | BT474 | SW620 | H460 | PC-3 | BXPC-3 | A431 | A549 | SKOV-3 | MDA-MB-468 | SKRB-3 | |
7d | 0.8 | 4.3 | 0.033 | 3.7 | 7.9 | 0.1 | 0.02 | 0.2 | 2.7 | 1.5 | 0.5 |
7e | 0.3 | 0.6 | 0.0043 | 0.3 | 6.0 | 0.3 | 0.2 | 0.044 | 0.4 | 0.9 | 0.0012 |
7f | 0.6 | 5.3 | 1.5 | 4.2 | 6.8 | 0.5 | 0.1 | 0.3 | 3.5 | 2.5 | 1.9 |
7i | 2.2 | 5.2 | 6.5 | 14.6 | 8.6 | 9.3 | 4.8 | 8.3 | 5.8 | 6.8 | 11.3 |
1 | 1.6 | >100 | 4.1 | 39.7 | 4.8 | 4.7 | 1.0 | 2.0 | 6.0 | 2.4 | 1.5 |
2 | 1.2 | 7.8 | 1.3 | 10.0 | 6.0 | 6.6 | 4.5 | 4.4 | 4.6 | 4.0 | 8.0 |
3. Experimental
3.1. General
3.2. Preparation of Compounds 4a–j
3.3. Preparation of Compounds 6a–j
3.4. General Procedure for Preparing Compounds 7a–t
3.5. Cell Culture
3.6. Cell Proliferation Assay (MTT Assay)
3.7. Apoptosis Analysis by Flow Cytometry (FCM)
4. Conclusions
Acknowledgements
References and Notes
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Shi, X.-H.; Wang, Z.; Xia, Y.; Ye, T.-H.; Deng, M.; Xu, Y.-Z.; Wei, Y.-Q.; Yu, L.-T. Synthesis and Biological Evaluation of Novel Benzothiazole-2-thiol Derivatives as Potential Anticancer Agents. Molecules 2012, 17, 3933-3944. https://doi.org/10.3390/molecules17043933
Shi X-H, Wang Z, Xia Y, Ye T-H, Deng M, Xu Y-Z, Wei Y-Q, Yu L-T. Synthesis and Biological Evaluation of Novel Benzothiazole-2-thiol Derivatives as Potential Anticancer Agents. Molecules. 2012; 17(4):3933-3944. https://doi.org/10.3390/molecules17043933
Chicago/Turabian StyleShi, Xuan-Hong, Zhao Wang, Yong Xia, Ting-Hong Ye, Mei Deng, You-Zhi Xu, Yu-Quan Wei, and Luo-Ting Yu. 2012. "Synthesis and Biological Evaluation of Novel Benzothiazole-2-thiol Derivatives as Potential Anticancer Agents" Molecules 17, no. 4: 3933-3944. https://doi.org/10.3390/molecules17043933