Non-Amine Based Analogues of Lavendustin A as Protein-Tyrosine Kinase Inhibitors

Mark S. Smyth, Irena Stefanova, Frank Hartmann, Ivan D. Horak, Nir Osherov, Alexander Levitzki, Terrence R. Burke

Research output: Contribution to journalArticlepeer-review


The fermentation product lavendustin A (1) is a protein-tyrosine kinase (PTK) inhibitor whose active pharmacophore has previously been shown to reside in the more simplified salicyl-containing benzylamine 2. Amine 2 bears some structural resemblance to two other natural product PTK inhibitors, erbstatin (3) and piceatannol (4). Non-amine containing analogues of 2 were therefore synthesized which incorporated additional aspects of either erbstatin or piceatannol. Examination of these inhibitors in immunoprecipitated p56lck, epidermal growth factor receptor (EGFR), and c-erb B-2/HER 2/neu PTK preparations showed that compound 12 (IC50 = 60 nM) was one of the most potent p56lck inhibitors reported to date. These results demonstrate that nitrogen is not an essential component of the lavendustin A pharmacophore 2 and that 1,2-diarylethanes and -ethenes bearing a salicyl moiety appear to be valuable structural motifs for the construction of extremely potent PTK inhibitors.

Original languageEnglish
Pages (from-to)3010-3014
Number of pages5
JournalJournal of Medicinal Chemistry
Issue number20
StatePublished - 1993
Externally publishedYes


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