Potencialis daganatellenes hatasu vegyuletek eloallitasa es vizsgalata

Translated title of the contribution: Preparation and characterization of potentional antitumor agents

László Orfi, Frigyes Wáczek, Mónika Szabó, István Kövesdi, György Mészáros, Miklós Idei, Anikó Horváth, Ferenc Hollósy, Marianna Mák, Zsolt Szegedi, Béla Szende, György Kéri, Béla Noszál

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2 Citations (Scopus)

Abstract

A parallel combinatorial library of over sixteen hundred compounds has been designed and synthesized for the development of new potential peptidomimetic protein tyrosine kinase (PTK) inhibitor leads that is aimed for intervening with the substrate binding site of the pp60(c-src) enzyme. The new structures were based on known PTK inhibitors having at least two variously substituted aromatic moieties attached by spacer groups of different length and flexibility. Eleven bis-aryl type inhibitory compounds were found in the range of 18-100 micromolar IC50 concentrations from combinations of twelve different substituents. Molecular modeling of the active compounds showed a characteristic distance of 13-14 Å between the farthest sp2 carbon atoms of the two aromatic rings. Conformational analysis, of several peptide substrates recently found for pp60(c-src) PTK [5,6,7] showed that the energy minimized conformers had the same distance between two aromatic moieties. Several compounds in the library not only showed remarkable PTK inhibitory activity but also a significant apoptosis inducing effect on HT-29 human colon tumor cells.

Original languageHungarian
Pages (from-to)115-122
Number of pages8
JournalActa pharmaceutica Hungarica
Volume69
Issue number3
Publication statusPublished - Jun 1 1999

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ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Orfi, L., Wáczek, F., Szabó, M., Kövesdi, I., Mészáros, G., Idei, M., Horváth, A., Hollósy, F., Mák, M., Szegedi, Z., Szende, B., Kéri, G., & Noszál, B. (1999). Potencialis daganatellenes hatasu vegyuletek eloallitasa es vizsgalata. Acta pharmaceutica Hungarica, 69(3), 115-122.