Dihydropyrimidine derivatives as MDM2 inhibitors.
Dihydropyrimidine (DHPM)
MDM2 inhibitor
cytotoxicity
in silico
Journal
Chemical biology & drug design
ISSN: 1747-0285
Titre abrégé: Chem Biol Drug Des
Pays: England
ID NLM: 101262549
Informations de publication
Date de publication:
27 Nov 2023
27 Nov 2023
Historique:
revised:
22
08
2023
received:
14
06
2023
accepted:
07
11
2023
pubmed:
28
11
2023
medline:
28
11
2023
entrez:
27
11
2023
Statut:
aheadofprint
Résumé
One of the chief pathways to regulate p53 levels is MDM2 protein, which negatively controls p53 by direct inhibition. Many cancers overproduce MDM2 protein to interrupt p53 functions. Therefore, impeding MDM2's binding to p53 can reactivate p53 in tumor cells may suggest an effective approach for tumor therapy. Here, some Monastrol derivatives were designed in silico as MDM2 inhibitors, and their initial cytotoxicity was evaluated in vitro on MFC-7 and MDA-MB-231 cells. A small library of Monastrol derivatives was created, and virtual screening (VS) was performed on them. The first-ranked compound, which was extracted from VS, and the other six compounds 5a-5f were selected to carry out the single-docking and docking with explicit waters. The compound with the best average results was then subjected to molecular dynamic (MD) simulation. Compounds 5a-5f were chemically synthesized and evaluated in vitro for their initial cytotoxicity on MFC-7 and MDA-MB-231 cells by MTT assay. The best compound was compound 5d with ΔG
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14399Informations de copyright
© 2023 John Wiley & Sons Ltd.
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