Isolation and characterization of cytotoxic cyclotides from Viola tricolor.
Many plants of the Violaceae plant family have been used in traditional remedies, and these plants often contain cyclotides, a particular type of plant cyclopeptide that is distinguished by a cyclic cystine knot motif. In general, bioactive plant cyclopeptides are interesting candidates for drug development. In the current study, a suite of 14 cyclotides, which includes seven novel cyclotides [vitri B, C, D, E, F, varv Hm, and He], together with seven known cyclotides [varv A, D, E, F, H, vitri A, and cycloviolacin O2], was isolated from Viola tricolor, a common flower. A chromatography-based method was used to isolate the cyclotides, which were characterized using tandem mass spectrometry and NMR spectroscopy. Several of the cyclotides showed cytotoxic activities against five cancer cell lines, U251, MDA-MB-231, A549, DU145, and BEL-7402. Three cyclotides, vitri A, vitri F, and cycloviolacin O2, were the most cytotoxic. The cytotoxic activity of the cyclotides did not correlate well with their hemolytic activity, indicating that different interactions, most likely with membranes, are involved for cytotoxic and hemolytic activities. Homology modeling of the structures was used in deriving structure-activity relationships.
Tang
Jun
J
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, 132# Lanhei Road, Heilongtan, Kunming 650204, Yunnan, PR China.
Wang
Conan K
CK
Pan
Xulin
X
Yan
He
H
Zeng
Guangzhi
G
Xu
Wenyan
W
He
Wenjun
W
Daly
Norelle L
NL
Craik
David J
DJ
Tan
Ninghua
N
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D047169:Cyclotides / Q000009:adverse effects / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D047168:Cystine Knot Motifs; D055808:Drug Discovery; D004365:Drugs, Chinese Herbal; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D035261:Plant Components, Aerial / Q000378:metabolism; D010940:Plant Proteins / Q000009:adverse effects / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013499:Surface Properties; D032413:Viola / Q000378:metabolism*
D000970:Antineoplastic Agents; D047169:Cyclotides; D004365:Drugs, Chinese Herbal; D010940:Plant Proteins; C473355:cycloviolacin O2