title: Isolation and Structure Elucidation by LC-DAD-MS and LC-DAD-SPE-NMR of Cyclopeptide Alkaloids from the Roots of Ziziphus oxyphylla and Evaluation of Their Antiplasmodial Activity.
abstract: Nine cyclopeptide alkaloids (1-9), of which five (compounds 2, 3, 5, 8, and 9) are described herein for the first time, were isolated from roots of Ziziphus oxyphylla by means of conventional separation methods as well as semipreparative HPLC with DAD and ESIMS detection and LC-DAD-SPE-NMR. Structure elucidation was done by spectroscopic means. Nummularine-R (1), a previously known constituent from this species, was isolated along with its new derivatives O-desmethylnummularine-R (2) and O-desmethylnummularine-R N-oxide (3). In addition, the known compounds hemsine-A (4) and ramosine-A (6), as well as hemsine-A N-oxide (5), were isolated. Moreover, oxyphylline-C (7), a known constituent of Z. oxyphylla stems, was obtained, and two new compounds were identified, oxyphyllines-E (8) and -F (9). Just like oxyphylline-C, oxyphyllines-E and -F belong to the relatively rare class of neutral cyclopeptide alkaloids. The antiplasmodial activity and cytotoxicity of compounds 1, 2, 4, 6, and 9 were evaluated, and the most promising activity was found for O-desmethylnummularine-R (2), which exhibited an IC50value of 3.2 ± 2.6 μM against Plasmodium falciparum K1, whereas an IC50value of >64.0 μM was evident for its cytotoxicity against MRC-5 cells.
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, and ‡Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp , Universiteitsplein 1, 2610 Antwerp, Belgium.
authors.forename: Emmy
authors.initials: E
authors.lastname: Tuenter
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, and ‡Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp , Universiteitsplein 1, 2610 Antwerp, Belgium.
authors.forename: Rizwan
authors.initials: R
authors.lastname: Ahmad
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, and ‡Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp , Universiteitsplein 1, 2610 Antwerp, Belgium.
authors.forename: Kenn
authors.initials: K
authors.lastname: Foubert
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, and ‡Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp , Universiteitsplein 1, 2610 Antwerp, Belgium.
authors.forename: Adnan
authors.initials: A
authors.lastname: Amin
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, and ‡Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp , Universiteitsplein 1, 2610 Antwerp, Belgium.
authors.forename: Maria
authors.initials: M
authors.lastname: Orfanoudaki
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, and ‡Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp , Universiteitsplein 1, 2610 Antwerp, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Cos
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, and ‡Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp , Universiteitsplein 1, 2610 Antwerp, Belgium.
authors.forename: Louis
authors.initials: L
authors.lastname: Maes
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, and ‡Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp , Universiteitsplein 1, 2610 Antwerp, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Apers
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, and ‡Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp , Universiteitsplein 1, 2610 Antwerp, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Pieters
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, and ‡Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp , Universiteitsplein 1, 2610 Antwerp, Belgium.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Exarchou
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002853:Chromatography, Liquid; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010154:Pakistan; D010456:Peptides, Cyclic / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives / Q000737:chemistry; D031957:Ziziphus / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D000962:Antimalarials; D010456:Peptides, Cyclic; D013806:Theophylline; C008749:etofylline