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Molecules 2017, 22(10), 1635; doi:10.3390/molecules22101635

A New Series of Cytotoxic Pyrazoline Derivatives as Potential Anticancer Agents that Induce Cell Cycle Arrest and Apoptosis

1
Department of Chemistry, Shantou University Medical College, Shantou 515041, Guangdong, China
2
Department of Pharmacy, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 12 September 2017 / Accepted: 26 September 2017 / Published: 29 September 2017
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Abstract

A new series of pyrazoline derivatives 1b12b was designed, synthesized and evaluated for antiproliferative activity against three cancer cell lines (HepG-2, Hela and A549). Additionally, NIH/3T3 cell cytotoxicity were tested and the structure activity relationships (SARs) were also determined. Among these new derivatives, the compounds 3-(4-fluorophenyl)-5-(3,4,5-trimethoxythiophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (1b) and 3-(4-chlorophenyl)-5-(3,4,5-trimethoxythiphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (2b) showed the best activity against HepG-2 cells, with IC50 values of 6.78 μM and 16.02 μM, respectively. They also displayed potent activity against Hela cells; meanwhile, 3-(4-chlorophenyl)-5-(3-bromo-4-hydroxy-5-methoxythiophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (5b) and 3-(4-bromo-phenyl)-5-(3-bromo-4-hydroxy-5-methoxythiophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (6b) were also identified as promising anticancer agents against A549 cells owing to their notable inhibitory effect, compared with cisplatin (IC50 = 29.48 μM). Furthermore, it was also found that compounds 1b and 2b had low cytotoxicity against NIH/3T3 cells and further mechanistic studies revealed that 1b arrested HepG-2 cells cycle at the G2/M phase at high concentrations and induced apoptosis in HepG-2 cells. Moreover, 1b upregulated protein expression level of cleaved caspase-3, cleaved PARP, Bax and p53 and downregulated protein expression level of Bcl-2 in dose-dependent way in HepG-2 cells. Thus, this study indicates that compound 1b might be a promising antitumor drug candidate. View Full-Text
Keywords: pyrazoline; antiproliferative; cytotoxicity; cell cycle arrest; apoptosis pyrazoline; antiproliferative; cytotoxicity; cell cycle arrest; apoptosis
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Wang, H.; Zheng, J.; Xu, W.; Chen, C.; Wei, D.; Ni, W.; Pan, Y. A New Series of Cytotoxic Pyrazoline Derivatives as Potential Anticancer Agents that Induce Cell Cycle Arrest and Apoptosis. Molecules 2017, 22, 1635.

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