Structural modifications of bryostatin 2.

Abstract

Continuation of a structure/activity relationship study of the bryostatins was focused on bryostatin 2. Stepwise catalytic hydrogenation of bryostatin 2 gave the following results. Reduction of the side-chain diene system to saturated ester 2a (P388 cell line ED50 8.5 x 10(-3) micrograms/ml) did not significantly affect the murine P388 cell line inhibition by bryostatin 2. Further hydrogenation to hexahydro derivative 2b gave a reduced P388 ED50 of 5.1 x 10(-2) micrograms/ml. Conversion to the octahydrobryostatin 2c caused a further reduction of P388 cell line activity to ED50 2.9 x 10(-1) micrograms/ml. Other structural modifications of bryostatin 2 in respect to esterification at the C-7 position significantly affected the P388 lymphocytic leukemia cell line response. Each of the bryostatin 2 derivatives was also evaluated with respect to protein kinase C binding.

• Authors: G R Pettit, D Sengupta, P M Blumberg, N E Lewin, J M Schmidt, A S Kraft
• Journal: Anti-cancer drug design (Anticancer Drug Des) Vol. 7 Issue 2 Pg. 101-14 (Apr 1992) ISSN: 0266-9536 [Print] United States
• PMID: 1575884 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Bryostatins
• Lactones
• Macrolides
• bryostatin 2
• Protein Kinase C

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Bryostatins
• Lactones (chemistry, pharmacology)
• Leukemia P388 (pathology)
• Macrolides
• Magnetic Resonance Spectroscopy
• Protein Kinase C (metabolism)
• Structure-Activity Relationship
• Tumor Cells, Cultured (drug effects)