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Research Article

Syringolin B-inspired proteasome inhibitor analogue TIR-203 exhibits enhanced biological activity in multiple myeloma and neuroblastoma

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Pages 25-29 | Received 10 Sep 2011, Accepted 21 Sep 2011, Published online: 23 Dec 2011

Figures & data

Figure 1.  The chemical structures of (A) syringolin A (SylA), (B) syringolin B (SylB), (C) glidobactin A (GlbA), and (D) syringolin B analogue TIR-203.

Figure 1.  The chemical structures of (A) syringolin A (SylA), (B) syringolin B (SylB), (C) glidobactin A (GlbA), and (D) syringolin B analogue TIR-203.

Figure 2.  Syringolin B-analogue TIR-203 inhibits the proliferation of human multiple myeloma (MM) cells and human neuroblastoma (NB) cells. (A) MM.1R cells and (B) MYCN2 cells were treated over a period of 24 h with natural product derived syringolin B-analogue TIR-203 at various concentrations (0–10 µM). SylA and bortezomib (Btz) were used as controls for comparison. The viability of cells is expressed as percent (%) cell survival relative to untreated control cells and was determined by MTS assay as outlined in the material and methods.

Figure 2.  Syringolin B-analogue TIR-203 inhibits the proliferation of human multiple myeloma (MM) cells and human neuroblastoma (NB) cells. (A) MM.1R cells and (B) MYCN2 cells were treated over a period of 24 h with natural product derived syringolin B-analogue TIR-203 at various concentrations (0–10 µM). SylA and bortezomib (Btz) were used as controls for comparison. The viability of cells is expressed as percent (%) cell survival relative to untreated control cells and was determined by MTS assay as outlined in the material and methods.

Figure 3.  Inhibitory effects of syringolin B-analogue TIR-203 on proteasomal activity in multiple myeloma (MM) cells and neuroblastoma (NB) cells. The (A) chymotrypsin-like (CT-L), (B) caspase-like (C-L), and the trypsin-like (T-L) proteolytic activities of MM.1R and MYCN2 cells were measured. Cells were treated over a period of 2 h with natural product derived syringolin B-analogue TIR-203 at various concentrations (0–10 µM). SylA and bortezomib (Btz) were used as controls for comparison. The proteasomal activities were measured as outlined in the material and methods section.

Figure 3.  Inhibitory effects of syringolin B-analogue TIR-203 on proteasomal activity in multiple myeloma (MM) cells and neuroblastoma (NB) cells. The (A) chymotrypsin-like (CT-L), (B) caspase-like (C-L), and the trypsin-like (T-L) proteolytic activities of MM.1R and MYCN2 cells were measured. Cells were treated over a period of 2 h with natural product derived syringolin B-analogue TIR-203 at various concentrations (0–10 µM). SylA and bortezomib (Btz) were used as controls for comparison. The proteasomal activities were measured as outlined in the material and methods section.

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