Synthesis of Structural Analogues of Lyngbyatoxin A and Their Evaluation as Activators of Protein Kinase C

Alan P. Kozikowski, Patrick W. Shum, Alakananda Basu, John S. Lazo

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Syntheses of several new analogues of lyngbyatoxin A from a single common intermediate are described. These compounds bear a carbon chain at the 7-position of the indolactam V (ILV) nucleus which contains either a hydrophilic or a lipophilic group. The effect of these minor structural alterations on the ability of the ILV analogues to activate the enzyme protein kinase C (PKC) was determined by measuring the extent of phosphorylation of calf thymus histone (III-S). Introduction of a hydroxyl group on the C-7 appendage was found to dramatically decrease compound 3’s ability to activate PKC. This result is interpreted in terms of the decreased ability of 3 to associate with the membrane bilayer.

Original languageEnglish
Pages (from-to)2420-2430
Number of pages11
JournalJournal of Medicinal Chemistry
Volume34
Issue number8
DOIs
StatePublished - 1 Aug 1991

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