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-1a receptor with docking scores comparable with those of well-known agonists even though with a somewhat different binding mode.

Antiproliferative activity on human prostate carcinoma cell lines of new peptidomimetics containing the spiroazepinoindolinone scaffold / S. Pellegrino, M. Ruscica, P. Magni, G. Vistoli, M.L. Gelmi. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 21:17(2013 Sep 01), pp. 5470-5479. [10.1016/j.bmc.2013.06.006]

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

S. Pellegrino
Primo
;
M. Ruscica
Secondo
;
P. Magni;G. Vistoli
Penultimo
;
M.L. Gelmi
Ultimo
2013-09-01

Abstract

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-1a receptor with docking scores comparable with those of well-known agonists even though with a somewhat different binding mode.
Docking; Ghrelin; Peptidomimetics; Prostate cancer
Settore CHIM/06 - Chimica Organica
Settore CHIM/08 - Chimica Farmaceutica
Settore MED/04 - Patologia Generale
Settore MED/05 - Patologia Clinica
Settore MED/13 - Endocrinologia
Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/223506
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