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Design, Synthesis and Biological Evaluation of a New Series of 1-Aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea Derivatives as Antiproliferative Agents.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2019 Jun 04; Vol. 24 (11). Date of Electronic Publication: 2019 Jun 04. - Publication Year :
- 2019
-
Abstract
- To discover new antiproliferative agents with high efficacy and selectivity, a new series of 1-aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea derivatives ( 7a - 7t ) were designed, synthesized and evaluated for their antiproliferative activity against A549, HCT-116 and PC-3 cancer cell lines in vitro. Most of the target compounds demonstrated significant antiproliferative effects on all the selective cancer cell lines. Among them, the target compound, 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-{4-{{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}thio}phenyl}urea ( 7i ) was identified to be the most active one against three cell lines, which was more potent than the positive control with an IC <subscript>50</subscript> value of 1.53 ± 0.46, 1.11 ± 0.34 and 1.98 ± 1.27 μM, respectively. Further cellular mechanism studies confirmed that compound 7i could induce the apoptosis of A549 cells in a concentration-dependent manner and elucidated compound 7i arrests cell cycle at G1 phase by flow cytometry analysis. Herein, the studies suggested that the 1-aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea skeleton might be regarded as new chemotypes for designing effective antiproliferative agents.
- Subjects :
- Antineoplastic Agents chemical synthesis
Apoptosis drug effects
Cell Cycle drug effects
Cell Line, Tumor
Chemistry Techniques, Synthetic
Drug Screening Assays, Antitumor
Humans
Hydrogen Bonding
Molecular Structure
Phenylurea Compounds chemical synthesis
Spectrum Analysis
Structure-Activity Relationship
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacology
Drug Design
Phenylurea Compounds chemistry
Phenylurea Compounds pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 24
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 31167363
- Full Text :
- https://doi.org/10.3390/molecules24112108