Inhibition mechanism of naphthylphenylamine derivatives acting on the CDC25B dual phosphatase and analysis of the molecular processes involved in the high cytotoxicity exerted by one selected derivative in melanoma cells.
Amino Acid Sequence
Aniline Compounds
/ chemistry
Antineoplastic Agents
/ chemistry
Apoptosis
/ drug effects
Caspase 3
/ metabolism
Caspase 9
/ metabolism
Catalytic Domain
Cell Line, Tumor
Drug Screening Assays, Antitumor
Enzyme Inhibitors
/ chemistry
Humans
Melanoma
/ drug therapy
Mutation
Optical Imaging
Structure-Activity Relationship
cdc25 Phosphatases
/ antagonists & inhibitors
CDC25
anticancer agents
cytotoxicity
inhibition mechanism
melanoma
Journal
Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Titre abrégé: J Enzyme Inhib Med Chem
Pays: England
ID NLM: 101150203
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
entrez:
29
9
2020
pubmed:
30
9
2020
medline:
1
5
2021
Statut:
ppublish
Résumé
The dual phosphatases CDC25 are involved in cell cycle regulation and overexpressed in many tumours, including melanoma. CDC25 is a promising target for discovering anticancer drugs, and several studies focussed on characterisation of quinonoid CDC25 inhibitors, frequently causing undesired side toxic effects. Previous work described an optimisation of the inhibition properties by naphthylphenylamine (NPA) derivatives of NSC28620, a nonquinonoid CDC25 inhibitor. Now, the CDC25B•inhibitor interaction was investigated through fluorescence studies, shedding light on the different inhibition mechanism exerted by NPA derivatives. Among the molecular processes, mediating the specific and high cytotoxicity of one NPA derivative in melanoma cells, we observed decrease of phosphoAkt, increase of p53, reduction of CDC25 forms, cytochrome
Identifiants
pubmed: 32990107
doi: 10.1080/14756366.2020.1819257
pmc: PMC7580834
doi:
Substances chimiques
Aniline Compounds
0
Antineoplastic Agents
0
Enzyme Inhibitors
0
cdc25 Phosphatases
EC 3.1.3.48
Caspase 3
EC 3.4.22.-
Caspase 9
EC 3.4.22.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1866-1878Références
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