Back to Search
Start Over
(-)-Neocaryachine, an Antiproliferative Pavine Alkaloid from Cryptocarya laevigata, Induces DNA Double-Strand Breaks.
- Source :
-
Journal of natural products [J Nat Prod] 2017 Jan 27; Vol. 80 (1), pp. 220-224. Date of Electronic Publication: 2017 Jan 18. - Publication Year :
- 2017
-
Abstract
- Twelve benzylisoquinoline alkaloids, including pavine and phenanthroindolizidine types, were isolated from a MeOH/CH <subscript>2</subscript> Cl <subscript>2</subscript> 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 IC <subscript>50</subscript> 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.
- Subjects :
- Alkaloids chemistry
Alkaloids pharmacology
Antineoplastic Agents, Phytogenic chemistry
Antineoplastic Agents, Phytogenic pharmacology
Cell Line, Tumor
DNA metabolism
Dioxoles chemistry
Humans
Indolizines chemistry
Indolizines pharmacology
Molecular Structure
Phenanthrolines chemistry
Phenanthrolines pharmacology
Alkaloids isolation & purification
Antineoplastic Agents, Phytogenic isolation & purification
Cell Proliferation drug effects
Cryptocarya chemistry
DNA chemistry
Dioxoles isolation & purification
Dioxoles pharmacology
Indolizines isolation & purification
Phenanthrolines isolation & purification
Subjects
Details
- Language :
- English
- ISSN :
- 1520-6025
- Volume :
- 80
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of natural products
- Publication Type :
- Academic Journal
- Accession number :
- 28099003
- Full Text :
- https://doi.org/10.1021/acs.jnatprod.6b01153