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

Raffaella Cincinelli; Loana Musso; Lucio Merlini; Giuseppe Giannini; Loredana Vesci; Ferdinando M. Milazzo; Nives Carenini; Paola Perego; Sergio Penco; Roberto Artali; Franco Zunino; Claudio Pisano; Sabrina Dallavalle

doi:10.1016/j.bmc.2013.12.031

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

Raffaella Cincinelli, Loana Musso, Lucio Merlini, Giuseppe Giannini, Loredana Vesci, Ferdinando M. Milazzo, Nives Carenini, Paola Perego, Sergio Penco, Roberto Artali, Franco Zunino, Claudio Pisano, Sabrina Dallavalle

Fondazione IRCCS Istituto Nazionale dei Tumori

Research output: Contribution to journal › Article

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

Original language	English
Pages (from-to)	1089-1103
Number of pages	15
Journal	Bioorganic and Medicinal Chemistry
Volume	22
Issue number	3
DOIs	https://doi.org/10.1016/j.bmc.2013.12.031
Publication status	Published - Feb 1 2014

Keywords

7-Azaindoles
Antitumor
Molecular modelling
PARP inhibitors
Synthesis

ASJC Scopus subject areas

Pharmaceutical Science
Drug Discovery
Organic Chemistry
Molecular Medicine
Molecular Biology
Clinical Biochemistry
Biochemistry

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Cincinelli, R., Musso, L., Merlini, L., Giannini, G., Vesci, L., Milazzo, F. M., Carenini, N., Perego, P., Penco, S., Artali, R., Zunino, F., Pisano, C., & Dallavalle, S. (2014). 7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors. Bioorganic and Medicinal Chemistry, 22(3), 1089-1103. https://doi.org/10.1016/j.bmc.2013.12.031

7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors. / Cincinelli, Raffaella; Musso, Loana; Merlini, Lucio; Giannini, Giuseppe; Vesci, Loredana; Milazzo, Ferdinando M.; Carenini, Nives; Perego, Paola; Penco, Sergio; Artali, Roberto; Zunino, Franco; Pisano, Claudio; Dallavalle, Sabrina.

In: Bioorganic and Medicinal Chemistry, Vol. 22, No. 3, 01.02.2014, p. 1089-1103.

Research output: Contribution to journal › Article

Cincinelli, Raffaella ; Musso, Loana ; Merlini, Lucio ; Giannini, Giuseppe ; Vesci, Loredana ; Milazzo, Ferdinando M. ; Carenini, Nives ; Perego, Paola ; Penco, Sergio ; Artali, Roberto ; Zunino, Franco ; Pisano, Claudio ; Dallavalle, Sabrina. / 7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors. In: Bioorganic and Medicinal Chemistry. 2014 ; Vol. 22, No. 3. pp. 1089-1103.

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