Antiproliferative activity on human prostate carcinoma cell lines of new peptidomimetics containing the spiroazepinoindolinone scaffold

Peptidomimetics containing the spiroazepinoindolinone scaffold were designed and synthesized in order to ascertain their antiproliferative activity on the DU-145 human prostatic carcinoma cell line. Ethyl 2'-oxa-1,2,3,5,6,7-hexahydrospiro[4H-azepine-4,3'-3H-indole]-1'-carboxylate scaffold was functionalized at nitrogen azepino ring with Aib-(L/D)Trp-OH dipeptides. Combining the different stereochemistries of the scaffold and the tryptophan, diastereoisomeric peptidomimetics were prepared and tested. Their biological activity was evaluated by proliferation studies proving that the isomer containing S spiroazepino-indolinone scaffold and L tryptophan is the most active compound. Docking studies confirmed that the active peptidomimetic could bind the GHSR-la receptor with docking scores comparable with those of well-known agonists even though with a somewhat different binding mode. (C) 2013 Elsevier Ltd. All rights reserved.