Synthesis and biological evaluation of thiobenzanilides as anticancer agents
| Autor: | Yan-Ren Chen, Long-Sen Chang, Jeh-Jeng Wang, Wan-Ping Hu, Yi-Min Tsai, Yin-Kai Chen, Hsin-Su Yu, Chao-Cheng Liao |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
G2 Phase
Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Apoptosis Mitochondrion DNA Mitochondrial Biochemistry Structure-Activity Relationship chemistry.chemical_compound Adenosine Triphosphate Annexin Drug Discovery Tumor Cells Cultured Humans Cytotoxic T cell Anilides Propidium iodide Cytotoxicity Molecular Biology Cell Proliferation chemistry.chemical_classification Reactive oxygen species Molecular Structure Caspase 3 Cell Cycle Organic Chemistry Stereoisomerism Flow Cytometry Cell biology chemistry Cell culture Benzamides Mitochondrial Membranes Molecular Medicine Drug Screening Assays Antitumor Reactive Oxygen Species Cell Division |
| Zdroj: | Bioorganic & Medicinal Chemistry. 16:5295-5302 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2008.03.003 |
| Popis: | A series of novel thiobenzanilides is described. These compounds have been previously found to show strong biological activity such as antimycotic and antifungal actions. This is the first demonstration on the mechanism of the anticancer effect of thiobenzanilide agents (4a-c) on human melanoma A375 cells. The cytotoxic studies of compounds 4a-c on human melanoma A375 cells indicate thiobenzanilides induced higher cytotoxicity than nitrobenzanilides (3a-c). In addition, DNA flow cytometric analysis shows that 4a-c displays a significant G2/M phase arrest, which progresses to early apoptosis as detected by flow cytometry after double-staining with annexin V and propidium iodide (PI). Because cellular apoptosis is often preceded by the disruption of mitochondrial function, the assessment of mitochondrial function in 4a-c-treated cells is worthy of investigation. Our data revealed that treatment of A375 cells with 4a-c resulted in the loss of mitochondrial membrane potential (DeltaPsi(mt)), a reduction of ATP synthesis, increased reactive oxygen species (ROS) generation, and activation of caspase-3. Thus, we suggest that 4a-c agents are potent inducers of cell apoptosis in A375 cells. |
| Databáze: | OpenAIRE |
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