Discovery of benzamide-based PI3K/HDAC dual inhibitors with marked pro-apoptosis activity in lymphoma cells.


Journal

European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510

Informations de publication

Date de publication:
15 Dec 2023
Historique:
received: 01 08 2023
revised: 19 10 2023
accepted: 25 10 2023
medline: 27 11 2023
pubmed: 11 11 2023
entrez: 10 11 2023
Statut: ppublish

Résumé

Inhibition of PI3K and histone deacetylase (HDAC) activity simultaneously using a single molecule appears to be a promising approach for cancer treatment. Current PI3K/HDAC dual inhibitors commonly use hydroxamate moiety as zinc binding group, which lack HDAC isoform selectivity and have potential genotoxicity. In this study, a novel series of benzamide-based PI3K/HDAC dual inhibitors were rationally designed and synthesized. Representative compound PH14 showed potent inhibitory activity toward PI3Kα and HDAC3, with IC

Identifiants

pubmed: 37948955
pii: S0223-5234(23)00882-6
doi: 10.1016/j.ejmech.2023.115915
pii:
doi:

Substances chimiques

Antineoplastic Agents 0
Histone Deacetylase Inhibitors 0
Phosphatidylinositol 3-Kinases EC 2.7.1.-
Benzamides 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

115915

Informations de copyright

Copyright © 2023 Elsevier Masson SAS. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Jingjing Deng (J)

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China; CAS Key Laboratory of Tropical Marine BioResources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, 510301, China.

Baogeng Hou (B)

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.

Xiaohan Hou (X)

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.

Yuxin Chen (Y)

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.

Tao Zhang (T)

Bioland Laboratory (Guangzhou Regenerative Medicine and Health-Guangdong Laboratory), Guangzhou, 510530, China.

Hua Chen (H)

Bioland Laboratory (Guangzhou Regenerative Medicine and Health-Guangdong Laboratory), Guangzhou, 510530, China.

Yuanze Wang (Y)

Bioland Laboratory (Guangzhou Regenerative Medicine and Health-Guangdong Laboratory), Guangzhou, 510530, China.

Xiaoyang Li (X)

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China; Center for Targeted Protein Degradation and Drug Discovery, Ocean University of China, Qingdao, Shandong, 266003, China. Electronic address: lixiaoyang@ouc.edu.cn.

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Classifications MeSH