7-Azaindole-1-carboxamides were designed as a new class of PARP-1 inhibitors. The compounds displayed a variable pattern of target inhibition profile that, in part, paralleled the antiproliferative activity in cell lines characterized by homologous recombination defects. A selected compound (1l; ST7710AA1) showed significant in vitro target inhibition and capability to substantially bypass the multidrug resistance mediated by Pgp. In antitumor activity studies against the MX1 human breast carcinoma growth in nude mice, the compound exhibited an effect similar to that of Olaparib in terms of tumor volume inhibition when used at a lower dose than the reference compound. Treatment was well tolerated, as no deaths or significant weight losses were observed among the treated animals.
7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors / R. Cincinelli, L. Musso, L. Merlini, G. Giannini, L. Vesci, F.M. Milazzo, N. Carenini, P. Perego, S. Penco, R. Artali, F. Zunino, C. Pisano, S. Dallavalle. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 22:3(2014), pp. 1089-1103.
|Titolo:||7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors|
|Parole Chiave:||PARP inhibitors; Synthesis; Molecular modelling; 7-Azaindoles; Antitumor|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
Settore CHIM/08 - Chimica Farmaceutica
|Data di pubblicazione:||2014|
|Data ahead of print / Data di stampa:||22-dic-2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.bmc.2013.12.031|
|Appare nelle tipologie:||01 - Articolo su periodico|