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Jung, M. et al.

Jung, Brosch, Kölle, Scherf, Gerhäuser, Loidl,

Amide analogues of trichostatin A as inhibitors of histone deacetylase and inducers of terminal cell differentiation.

Inhibitors of histone deacetylase (HD) bear great potential as new drugs due to their ability to modulate transcription and to induce apoptosis or differentiation in cancer cells. We have described previously analogues of the complex natural HD inhibitors trapoxin B and trichostatin A with activities in the submicromolar range. Here we report structure-activity relationship analyses of further analogues of trichostatin A with respect to in vitro inhibition of maize HD-2 and their ability to induce terminal cell differentiation in Friend leukemic cells. This is the first report that shows the correlation between HD inhibitory activity and action on cancer cells on a larger series of similar compounds. Only the compounds that inhibit HD induce differentiation and/or exert antiproliferative activities in cell culture. Our studies support the use of in vitro systems as screening tools and provide structure-activity relationships that merit further investigation of this interesting target.[1]

References

Amide analogues of trichostatin A as inhibitors of histone deacetylase and inducers of terminal cell differentiation. Jung, M., Brosch, G., Kölle, D., Scherf, H., Gerhäuser, C., Loidl, P. J. Med. Chem. (1999) [Pubmed]

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