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

被引：43

作者：

Cincinelli, Raffaella ^{[1
]}

Musso, Loana ^{[1
]}

Merlini, Lucio ^{[1
]}

Giannini, Giuseppe ^{[2
]}

Vesci, Loredana ^{[2
]}

Milazzo, Ferdinando M. ^{[2
]}

Carenini, Nives ^{[3
]}

Perego, Paola ^{[3
]}

Penco, Sergio ^{[2
]}

Artali, Roberto ^{[4
]}

Zunino, Franco ^{[3
]}

Pisano, Claudio ^{[2
]}

Dallavalle, Sabrina ^{[1
]}

机构：

[1] Univ Milan, Dept Food Environm & Nutr Sci, Div Chem & Mol Biol, I-20133 Milan, Italy

[2] R&D Sigma Tau Ind Farmaceut Riunite SpA, I-00040 Pomezia, RM, Italy

[3] Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Mol Pharmacol Unit, I-20133 Milan, Italy

[4] Scientia Advice, I-20832 Desio, MB, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2014年 / 22卷 / 03期

关键词：

PARP inhibitors; Synthesis; Molecular modelling; 7-Azaindoles; Antitumor; DNA-REPAIR; DOCKING; CANCER; DERIVATIVES; COMPLEX; 3D-QSAR; DESIGN; FAMILY; SERIES; ROLES;

D O I：

10.1016/j.bmc.2013.12.031

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：1089 / 1103

页数：15

共 46 条

[1] Total syntheses of variolin B and deoxyvariolin B
Ahaidar, A
Fernández, D
Danelón, G
Cuevas, C
Manzanares, I
Albericio, F
Joule, JA
Alvarez, M
[J]. JOURNAL OF ORGANIC CHEMISTRY, 2003, 68 (26) : 10020 - 10029
[2] Potent nonclassical nucleoside antiviral drugs based on the N,N-diarylformamidine concept
Anastasi, C
Hantz, O
De Clercq, E
Pannecouque, C
Clayette, P
Dereuddre-Bosquet, N
Dormont, D
Gondois-Rey, F
Hirsch, I
Kraus, JL
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (05) : 1183 - 1192
[3] Docking studies on PARP-1 inhibitors: insights into the role of a binding pocket water molecule
Bellocchi, D
Macchiarulo, A
Costantino, G
Pellicciari, R
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2005, 13 (04) : 1151 - 1157
[4] Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
Bryant, HE
Schultz, N
Thomas, HD
Parker, KM
Flower, D
Lopez, E
Kyle, S
Meuth, M
Curtin, NJ
Helleday, T
[J]. NATURE, 2005, 434 (7035) : 913 - 917
[5] Synthesis and structure-activity relationships of a new series of retinoid-related biphenyl-4-ylacrylic acids endowed with antiproliferative and proapoptotic activity
Cincinelli, R
Dallavalle, S
Nannei, R
Carella, S
De Zani, D
Merlini, L
Penco, S
Garattini, E
Giannini, G
Pisano, C
Vesci, L
Carminati, P
Zuco, V
Zanchi, C
Zunino, F
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (15) : 4931 - 4946
[6] Modeling of poly(ADP-ribose)polymerase (PARP) inhibitors. Docking of ligands and quantitative structure-activity relationship analysis
Costantino, G
Macchiarulo, A
Camaioni, E
Pellicciari, R
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (23) : 3786 - 3794
[7] Therapeutic applications of PARP inhibitors: Anticancer therapy and beyond
Curtin, Nicola J.
Szabo, Csaba
[J]. MOLECULAR ASPECTS OF MEDICINE, 2013, 34 (06) : 1217 - 1256
[8] Curtin NJ, 2012, DRUG DISCOV TODAY, V9, P51
[9] Design, synthesis, and evaluation of biphenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors
Dallavalle, Sabrina
Cincinelli, Raffaella
Nannei, Raffaella
Merlini, Lucio
Morini, Gabriella
Penco, Sergio
Pisano, Claudio
Vesci, Loredana
Barbarino, Marcella
Zuco, Valentina
De Cesare, Michelandrea
Zunino, Franco
[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2009, 44 (05) : 1900 - 1912
[10] The diverse roles and clinical relevance of PARPs in DNA damage repair: Current state of the art
De Vos, Mike
Schreiber, Valerie
Dantzer, Francoise
[J]. BIOCHEMICAL PHARMACOLOGY, 2012, 84 (02) : 137 - 146

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