silicon and fosbretabulin

Silicon-containing combretastatin analogs were designed, synthesized and evaluated for stability and biological activities. Among them, compound 31 exhibited strong tubulin polymerization-inhibitory activity and very potent tumor cell growth-inhibitory activity (IC50=0.007 μM) in MCF-7 cell proliferation assay. This compound also potently inhibited [(3)H]colchicine binding (90.7% inhibition at 3 μM). These activities were comparable to those of combretastatin A-4 (CA-4) (1). In addition, compound 31 was physico-chemically more stable than 1. These results suggest that a silicon linker can act as a bioisoster of a cis carbon-carbon double bond.

Topics: Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Colchicine; Drug Design; Female; Humans; Silicon; Stilbenes; Tubulin; Tubulin Modulators

The present study evaluated the treatment efficacy of the vascular disrupting agents CA4P and OXi4503 in an orthotopically transplanted human renal cell carcinoma xenograft model (Caki-1). Experiments used vascular casting, vessel density assessments as well as tumour necrosis measurements to evaluate the efficacy of these agents. After treatment with either agent, assessment of the vascular casts showed an almost total eradication of tumour blood vessels. Histological evidence further supported this observation, showing extensive central tumour necrosis with only a small viable rim of tumour cells remaining at the periphery. These results suggest that vascular disrupting agents CA4P and OXi4503 may have utility in the treatment of renal cell carcinoma, an encouraging result given that current conventional therapies have been currently largely unsuccessful in managing this disease.

Topics: Angiogenesis Inhibitors; Animals; Carcinoma, Renal Cell; Diphosphates; Female; Humans; Kidney Neoplasms; Mice; Mice, Nude; Neoplasm Transplantation; Neovascularization, Pathologic; Silicon; Stilbenes; Transplantation, Heterologous