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. [10.1016/j.bmc.2013.12.031]

7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors

R. Cincinelli;L. Musso;L. Merlini;S. Dallavalle
2014

Abstract

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.
PARP inhibitors; Synthesis; Molecular modelling; 7-Azaindoles; Antitumor
Settore CHIM/06 - Chimica Organica
Settore CHIM/08 - Chimica Farmaceutica
22-dic-2013
Article (author)
File in questo prodotto:
File Dimensione Formato  
2014 7azaindoles.pdf

accesso aperto

Tipologia: Post-print, accepted manuscript ecc. (versione accettata dall'editore)
Dimensione 1.09 MB
Formato Adobe PDF
1.09 MB Adobe PDF Visualizza/Apri
1-s2.0-S0968089613010250-main.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 2.37 MB
Formato Adobe PDF
2.37 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/230356
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 35
  • ???jsp.display-item.citation.isi??? 37
social impact