Synthesis of phthalazine-based derivatives as selective anti-breast cancer agents through EGFR-mediated apoptosis: in vitro and in silico studies.
Apoptosis
EGFR-mediated
Phthalazine-based
Selective anti-breast
Journal
BMC chemistry
ISSN: 2661-801X
Titre abrégé: BMC Chem
Pays: Switzerland
ID NLM: 101741142
Informations de publication
Date de publication:
27 Jul 2023
27 Jul 2023
Historique:
received:
21
03
2023
accepted:
30
06
2023
medline:
28
7
2023
pubmed:
28
7
2023
entrez:
27
7
2023
Statut:
epublish
Résumé
The parent 2-(4-benzyl-1-oxophthalazin-2(1H)-yl)-acetohydrazide (4) has twenty-nine compounds. The starting material for their corresponding mono, dipeptides and reactions with active methylene compounds were produced by chemoselective N-alkylation of 4-Benzyl-2H-phthalazin-1-one (2) with ethyl chloroacetate to afford (4-benzyl-1-oxo-1H-phthalazin-2-yl) methyl acetate (3). The ester 3 was hydrazinolyzed to give hydrazide 4, then azide 5 coupled with amino acid ester hydrochloride and/or amines to produce several monopeptides, then the methyl (2-(4-benzyl-1-oxophthalazin-2(1H)-yl) acetyl) glycinate (7a) was hydrazinolyzed to produce corresponding hydrazide 2-(4-benzyl-1-oxophthalazin-2(1H)-yl)-N-(2-hydrazineyl-2-oxo ethyl) acetamide (8a). The hydrazide 8a under azide coupling method was coupled with amino acid ester hydrochloride and/or amines to produce several dipeptides, and the hydrazide 8a was also condensed and/or cyclized with several carbonyl compounds. The cytotoxicity of the synthesized compounds was tested using MTT assay, as well as apoptosis-induction through EGFR inhibition. Compounds 11d, 12c and 12d exhibited potent cytotoxic activities with IC
Identifiants
pubmed: 37501139
doi: 10.1186/s13065-023-00995-2
pii: 10.1186/s13065-023-00995-2
pmc: PMC10375784
doi:
Types de publication
Journal Article
Langues
eng
Pagination
90Informations de copyright
© 2023. The Author(s).
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