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

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)1089-1103
Number of pages15
JournalBioorganic and Medicinal Chemistry
Volume22
Issue number3
DOIs
Publication statusPublished - Feb 1 2014

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Homologous Recombination
Multiple Drug Resistance
Tumor Burden
Nude Mice
Tumors
Weight Loss
Animals
Cells
Breast Neoplasms
Cell Line
Defects
Growth
olaparib
Poly(ADP-ribose) Polymerase Inhibitors
7-azaindole dimer
In Vitro Techniques

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

Cite this

Cincinelli, R., Musso, L., Merlini, L., Giannini, G., Vesci, L., Milazzo, F. M., ... 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 journalArticle

Cincinelli, R, Musso, L, Merlini, L, Giannini, G, Vesci, L, Milazzo, FM, 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, vol. 22, no. 3, pp. 1089-1103. https://doi.org/10.1016/j.bmc.2013.12.031
Cincinelli R, Musso L, Merlini L, Giannini G, Vesci L, Milazzo FM et al. 7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors. Bioorganic and Medicinal Chemistry. 2014 Feb 1;22(3):1089-1103. https://doi.org/10.1016/j.bmc.2013.12.031
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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