Deletion of the C26 Methyl Substituent from the Bryostatin Analogue Merle23 Has Negligible Impact on Its Biological Profile and Potency

作者：Zhao Xiguang; Kedei Noemi; Michalowski Alexandra; Lewin Nancy E; Keck Gary E; Blumberg Peter M^*

来源：ChemBioChem, 2018, 19(10): 1049-1059.

DOI：10.1002/cbic.201700677

• drug design
• natural products
• protein kinaseC
• signal transduction
• structure-activity relationships

Important strides are being made in understanding the effects of structural features of bryostatin1, a candidate therapeutic agent for cancer and dementia, in conferring its potency toward protein kinaseC and the unique spectrum of biological responses that it induces. A critical pharmacophoric element in bryostatin1 is the secondary hydroxy group at the C26 position, with a corresponding primary hydroxy group playing an analogous role in binding of phorbol esters to protein kinase C. Herein, we describe the synthesis of a bryostatin homologue in which the C26 hydroxy group is primary, as it is in the phorbol esters, and show that its biological activity is almost indistinguishable from that of the corresponding compound with a secondary hydroxy group.

• 出版日期2018-5-18