Screening of peptidomimetic libraries for antitumor activity

The aim of our work was to screen peptidomimetic tyrosine kinase inhibitory libraries for antiproliferative and apoptotic or necrotic effect. We also wanted to distinguish between cytostatic and cytotoxic activities.4-Benzylaminoquinasolines can be potent reversible inhibitors of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase. It is known that after the benzylic methylation the biological activity depends on the chirality of the carbon atom, therefore we synthesized 4-amino acid quinasoline derivatives varying the nature and the configuration of the amino acid and/or the substituent of the benzyl ring (R2). A similar library was developed when we substituted quinasolone derivatives in position 2 with different amino acid derivatives. The synthesis of these libraries resulted in more then 100 compounds of each library. We systematically tested the above libraries using three different biologicalassays.1. MTT test: fast screening of big number of compounds for the inhibition of human carcinoma cell proliferation. 2. Counting of the cells: screening of the compounds which showed some biological activity in the previous assay. 3. Tyrosine kinase assay. The results of the above assays will be discussed.