| Autor: |
Mandal S; Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada., Bérubé G, Asselin E, Richardson VJ, Church JG, Bridson J, Pham TN, Pramanik SK, Mandal SK |
| Jazyk: |
angličtina |
| Zdroj: |
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2007 Apr 15; Vol. 17 (8), pp. 2139-45. Date of Electronic Publication: 2007 Feb 08. |
| DOI: |
10.1016/j.bmcl.2007.01.116 |
| Abstrakt: |
A novel class of platinum(II) complexes of pyridine sulfide derivatives of triazine was synthesized, characterized, and investigated using the human breast cancer cell line, MDA-MB-468. S-30 was one of the most potent derivatives of its class (IC(50), 0.39 microM) eliciting the greatest biological response. S-30 induced arrest in the G1 phase and apoptosis (TUNEL assay) in a p53/p21(WAF1/CIP1)-consistent manner. Modeling and docking experiments were performed for three known targets for cisplatin, d(GpG), d(ApG), and a protein (Cu/Zn superoxide dismutase, SOD) from bovine origin. A Blast search of bovine SOD was performed to identify analogous human protein targets resulting in about 22 human proteins. A multi-sequence alignment of those targets showed >80% sequence identity and >88% similarity. One of them is SOD1 that is differentially expressed (based on global gene expression pattern) in various forms of cancer and other diseases. SOD1 controls apoptosis via p53/BAD/BAX/BCL2 in the amyotrophic lateral sclerosis (ALS) pathway and is also involved in various other KEGG's pathways. Results suggest that the S-30 is a potential cytotoxic agent. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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