cycloviolacin-o2 and Hemolysis

Topics: Amino Acid Sequence; Antineoplastic Agents, Phytogenic; Biodiversity; Cell Line, Tumor; Cyclotides; Drug Screening Assays, Antitumor; Female; HeLa Cells; Hemolysis; Humans; Male; Molecular Structure; Plant Extracts; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Vietnam; Viola

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.

Topics: Amino Acid Sequence; Antineoplastic Agents; Cyclotides; Cystine Knot Motifs; Drug Discovery; Drugs, Chinese Herbal; Hemolysis; Humans; Hydrophobic and Hydrophilic Interactions; Inhibitory Concentration 50; Models, Molecular; Molecular Sequence Data; Molecular Weight; Plant Components, Aerial; Plant Proteins; Sequence Homology, Amino Acid; Structure-Activity Relationship; Surface Properties; Viola