Structural modifications of bryostatin 2

George Pettit; D. Sengupta; P. M. Blumberg; N. E. Lewin; J. M. Schmidt; A. S. Kraft

Structural modifications of bryostatin 2

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

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Pages (from-to)	101-114
Number of pages	14
Journal	Anti-Cancer Drug Design
Volume	7
Issue number	2
State	Published - 1992

ASJC Scopus subject areas

Biochemistry
Oncology
General Biochemistry, Genetics and Molecular Biology
Pharmacology
Drug Discovery
Organic Chemistry

Cite this

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title = "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 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.",

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TY - JOUR

T1 - Structural modifications of bryostatin 2

AU - Pettit, George

AU - Sengupta, D.

AU - Blumberg, P. M.

AU - Lewin, N. E.

AU - Schmidt, J. M.

AU - Kraft, A. S.

PY - 1992

Y1 - 1992

N2 - 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.

AB - 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.

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JO - Anti-Cancer Drug Design

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Structural modifications of bryostatin 2

Abstract

ASJC Scopus subject areas

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