Structural modifications of bryostatin 2

G. R. Pettit, D. Sengupta, P. M. Blumberg, N. E. Lewin, J. M. Schmidt, A. S. Kraft

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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 μg/ml) did not significantly affect thc 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 μg/ml. Conversion to the octahydrobryostatin 2c caused a further reduction of P388 cell line activity to ED50 2.9 x 10-1 μg/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.

Original languageEnglish (US)
Pages (from-to)101-114
Number of pages14
JournalAnti-Cancer Drug Design
Volume7
Issue number2
StatePublished - Jan 1 1992

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ASJC Scopus subject areas

  • Biochemistry
  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Pettit, G. R., Sengupta, D., Blumberg, P. M., Lewin, N. E., Schmidt, J. M., & Kraft, A. S. (1992). Structural modifications of bryostatin 2. Anti-Cancer Drug Design, 7(2), 101-114.