Design, synthesis and cytotoxic activities of novel 2,5-diketopiperazine derivatives.
Eur J Med Chem
; 121: 500-509, 2016 Oct 04.
Article
in En
| MEDLINE
| ID: mdl-27318124
ABSTRACT
A series of novel N-1-monoallylated 2,5-diketopiperazine derivatives were designed, synthesized, and evaluated as cytotoxic agents against eight cancer cell lines by using CCK8 assay. These derivatives were substituted with methoxyphenyl groups at C-6 position, and various long alkyl side chains at C-3-position of the 2,5-diketopiperazine ring. The cytotoxic results showed that 4-methoxyphenyl group was better than 2-methoxyphenyl group as optimal substitutive group, while 3-methoxyphenyl group was not a suitable one. When the number (n value) of the methylene groups for the long alkyl side chain was 3 (compounds 1c and 3c), the derivatives had the strongest cytotoxicities. Compound 3c substituted with 4-methoxyphenyl group and pentylidene side chain exhibited strong activity (IC50 = 0.36-1.9 µM) against all cancer cell lines, and could obviously induce apoptosis of cancer cell line U937 at 1.0 µM after 48 h treatment.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug Design
/
Diketopiperazines
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Eur J Med Chem
Year:
2016
Document type:
Article
Affiliation country:
China