(-)-Neocaryachine, an Antiproliferative Pavine Alkaloid from Cryptocarya laevigata, Induces DNA Double-Strand Breaks.
J Nat Prod
; 80(1): 220-224, 2017 01 27.
Article
in En
| MEDLINE
| ID: mdl-28099003
ABSTRACT
Twelve benzylisoquinoline alkaloids, including pavine and phenanthroindolizidine types, were isolated from a MeOH/CH2Cl2 extract of Cryptocarya laevigata (stem bark) through bioactivity-guided fractionation for antitumor effects. Selected compounds were evaluated for antiproliferative activity against five human tumor cell lines, including a multidrug-resistant subline. Since more common 2,3,8,9-tetrasubstituted pavine alkaloids, such as crychine (3), exhibit very mild or no cytotoxicity, this compound type has not been well investigated for antitumor activity. Thus, this report is the first discovery of a 7-hydroxylated pavine alkaloid, (-)-neocaryachine (1), to demonstrate strong antiproliferative activity, with IC50 values of 0.06 to 0.41 µM against five tested tumor cell lines, including an MDR subline. Further mechanism of action studies revealed that 1 impacts the cellular S-phase by inducing DNA double-strand breaks.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phenanthrolines
/
DNA
/
Cryptocarya
/
Cell Proliferation
/
Dioxoles
/
Alkaloids
/
Indolizines
/
Antineoplastic Agents, Phytogenic
Limits:
Humans
Language:
En
Journal:
J Nat Prod
Year:
2017
Document type:
Article
Affiliation country:
Japan