Bioorganic & medicinal chemistry letters, 2015-02, Vol.25 (3), p.654-658
2015
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Details
- Autor(en) / Beteiligte
- Titel
- Synthesis and anticancer evaluation of novel triazole linked N-(pyrimidin-2-yl)benzo[d]thiazol-2-amine derivatives as inhibitors of cell survival proteins and inducers of apoptosis in MCF-7 breast cancer cells
- Ist Teil von
- Bioorganic & medicinal chemistry letters, 2015-02, Vol.25 (3), p.654-658
- Ort / Verlag
- England: Elsevier Ltd
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- [Display omitted] •A series of novel triazole linked N-(pyrimidin-2yl)benzo[d]thiazol-2-amine derivatives were synthesized.•Synthesized compounds were evaluated for anticancer activity and cytotoxic effects were compared against normal breast epithelial cells.•Treatment of MCF-7 cells with these compounds resulted in G2/M cell cycle arrest.•Compounds inhibit the proteins responsible for cell proliferation (ERK1/2) and confer resistance to apoptotic induction.•These hybrids cause apoptosis through caspase-9 induction. A series of novel triazole linked N-(pyrimidin-2yl)benzo[d]thiazol-2-amine 5a–k were synthesized and evaluated for anticancer activity against breast (MCF-7), lung (A549) and skin (A375) cancer cell lines and their cytotoxic effects were compared against normal breast epithelial cells. The effect of compounds on cell cycle of MCF-7 breast cancer cell line was investigated by FACS. Result indicated G2/M cell cycle arrest of MCF-7 cells. Further promising compounds 5b, 5g, 5h and 5i were tested for their apoptosis inducing ability as well as inhibitory activity against key proteins NF-kB, Survivin, CYP1A1, and ERK1/2 which help in cancer cell survival and proliferation. The apoptotic aspect of these compounds is further evidenced by increase in the activity of caspase-9 in MCF-7 cells. Hence these small molecules have the potential to control both the cell proliferation as well as the invasion process in highly malignant breast cancers and can be selected for further biological studies.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0960-894XeISSN: 1464-3405DOI: 10.1016/j.bmcl.2014.11.083Titel-ID: cdi_proquest_miscellaneous_1660394544
- Format
- –
- Schlagworte
- Antineoplastic Agents - chemical synthesis, Antineoplastic Agents - chemistry, Antineoplastic Agents - toxicity, Apoptosis - drug effects, Breast cancer cells, Caspase 9 - metabolism, Cell Line, Tumor, Cell Survival - drug effects, Cytochrome P-450 CYP1A1 - antagonists & inhibitors, Cytochrome P-450 CYP1A1 - metabolism, Cytotoxicity, G2 Phase Cell Cycle Checkpoints - drug effects, Humans, M Phase Cell Cycle Checkpoints - drug effects, MCF-7 Cells, Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors, Mitogen-Activated Protein Kinase 1 - metabolism, Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors, Mitogen-Activated Protein Kinase 3 - metabolism, N-(Pyrimidin-2yl)benzo[d]thiazol-2-amine, NF-kappa B - antagonists & inhibitors, NF-kappa B - metabolism, Pyrimidines - chemistry, Sharpless conditions, Structure-Activity Relationship, Thiazoles - chemical synthesis, Thiazoles - chemistry, Thiazoles - toxicity, Triazole, Triazoles - chemistry