Design, synthesis and evaluation of phthalazinone thiohydantoin-based derivative as potent PARP-1 inhibitors.
Antineoplastic Agents
/ chemistry
Breast Neoplasms
/ drug therapy
Cell Cycle
Cell Proliferation
Drug Design
Female
Humans
Imidazoles
/ chemical synthesis
Molecular Structure
Phthalazines
/ chemistry
Poly (ADP-Ribose) Polymerase-1
/ antagonists & inhibitors
Poly(ADP-ribose) Polymerase Inhibitors
/ chemical synthesis
Structure-Activity Relationship
Thiohydantoins
/ chemistry
Tumor Cells, Cultured
Antitumor
Chemosensitizer
Inhibitor
PARP-1
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
14
01
2019
revised:
28
06
2019
accepted:
01
08
2019
pubmed:
14
8
2019
medline:
21
10
2020
entrez:
13
8
2019
Statut:
ppublish
Résumé
Two new series of compounds were designed and synthesized as potent PARP-1 inhibitors. These compounds were evaluated for PARP-1 enzyme and cellular inhibitory activities. All efforts lead to the identification of 9k (named as LG-12) with efficient potency both for PARP-1 and BRCA1 deficient MDA-MB-436 cells. Additionally, the novel PARP-1 inhibitor LG-12 is an efficient chemosensitizer, which could potentiate the anti-cancer effect of TMZ. Our data presented herein provide a comprehensive preclinical in vitro evaluation of the potential therapeutic efficacy and potency of chemotherapeutic agent-PARP-1 inhibitor combinations for LG-12. The combined results indicated that LG-12 could be a promising candidate for further study.
Identifiants
pubmed: 31404795
pii: S0045-2068(19)30065-3
doi: 10.1016/j.bioorg.2019.103181
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Imidazoles
0
Phthalazines
0
Poly(ADP-ribose) Polymerase Inhibitors
0
Thiohydantoins
0
PARP1 protein, human
EC 2.4.2.30
Poly (ADP-Ribose) Polymerase-1
EC 2.4.2.30
Types de publication
Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
103181Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.