التفاصيل البيبلوغرافية
| العنوان: |
Antineoplastic Agents. 509. Synthesis of Fluorcombstatin Phosphate and Related 3-Halostilbenes,1 |
| المؤلفون: |
Pettit, G. R., Minardi, M. D., Rosenberg, H. J., Hamel, E., Bibby, M. C., Martin, S. W., Jung, M. K., Pettit, R. K., Cuthbertson, T. J., Chapuis, J.-C. |
| المصدر: |
Journal of Natural Products; October 2005, Vol. 68 Issue: 10 p1450-1458, 9p |
| مستخلص: |
The present SAR study of combretastatin A-3 (3a) focused on replacement of the 3-hydroxyl group by a series of halogens. That approach with Z-stilbenes resulted in greatly enhanced (>10−100-fold) cancer cell growth inhibition against a panel of human cancer cell lines and the murine P388 lymphocytic leukemia cell line. Synthesis of the 3-fluoro-Z-stilbene designated fluorcombstatin (11a) and its potassium 3-O-phosphate derivative (16c) by the route 7 → 8a → 11a → 14 → 16c illustrates the general synthetic pathway. The 3-O-phosphoric acid ester (15) of 3-bromo-Z-stilbene 13a was also converted to representative cation salts to evaluate the potential for improved aqueous solubility, and the potassium salt (16 mg/mL in water) proved most useful. The fluoro (11a), chloro (12a), and bromo (13a) halocombstatins were nearly equivalent to combretastatin A-4 (1a) as inhibitors of tubulin polymerization and of the binding of colchicine to tubulin. The tubulin binding in cell-free systems was also retained in human umbilical vein endothelial cells. All three halocombstatins retained the powerful human cancer cell line inhibitory activity of combretastatin A-4 (1a) and proved superior to combretastatin A-3 (3a). In addition, the halocombstatins targeted Gram-positive bacteria and Cryptococcus neoformans. |
| قاعدة البيانات: |
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