Phytochemical characterization and biological activity of secondary metabolites from three Limonium species

Authors: GADETSKAYA, ANASTASSIYA - University Of Mississippi; MOHAMED, SHAYMAA - University Of Mississippi; TARAWNEH, AMER - University Of Mississippi; MOHAMED, NESMA - University Of Mississippi; MA, GUOYI - University Of Mississippi; PONOMAREV, BORIS - Almaty; ZHUSUPOVA, GALIYA - Almaty; Cantrell, Charles; CUTLER, STEPHEN - University Of Mississippi; ROSS, SAMIR - University Of Mississippi

Submitted to: Medicinal Chemistry Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/26/2017
Publication Date: 7/12/2017
Publication URL: https://handle.nal.usda.gov/10113/6472279
Citation: Gadetskaya, A.V., Mohamed, S.M., Tarawneh, A.H., Mohamed, N.M., Ma, G., Ponomarev, B.N., Zhusupova, G.E., Cantrell, C.L., Cutler, S.J., Ross, S.A. 2017. Phytochemical characterization and biological activity of secondary metabolites from three Limonium species. Medicinal Chemistry Research. 26:2743-2750. 10.1007/s00044-017-1973-z.
DOI: https://doi.org/10.1007/s00044-017-1973-z

Interpretive Summary: The genus Limonium includes over 300 species world-wide, of which 18 are found in Kazakhstan. Several species of the Limonium genus have potential scientific, pharmacological and medical uses. Previous phytochemical and biological studies on the Limonium genus demonstrated the presence different classes of biologically active compounds. As a part of our search for novel, plant-derived biological agents, L myrianthum, L leptophyllum and L gmelinii were studied. The aim of the present study was to investigate the constituent of these three Limonium sp. aerial parts and/or roots. Herein, we report the isolation of a new natural product, with potent activity against malaria, along with eight known compounds from L leptophyllum. Another twelve known compounds were isolated from L myrianthum, and six known compounds isolated from L gmelinii. Chemical similarities among the three species were observed; however, each species displayed differences in phytochemical constituents. All isolated compounds were evaluated for their antimalarial, antileishmanial, antimicrobial and cytotoxic activities.

Technical Abstract: Plant tissues typically contain a diverse complement of secondary metabolites that provide protection against various biotic and abiotic hazards. Chemical similarities are commonly used to interpret phylogenetic relationships among plant taxa. The comparative phytochemical constituents of three Limonium species (L myrianthum, L leptophyllum and L gmelinii) were elucidated and characterized. Chemical similarities among the three species were observed; however, each species displayed differences in phytochemical constituents. Limonium leptophyllum extract resulted in the isolation of one new compound: (2R,3S)-2,3,4-trihydroxy-2-methylbutyl gallate (1), together with emodin (2), bergenin (3), mahuannin B (4), 7-O-galloyl-D-sedoheptulose (5), arbutin (6), gallic acid-4-O-ß-D-glucoside (7), myricetin (8), and myricetin-3-O-L-rhamnopyranoside (9). Both L myrianthum and L gmelinii showed some similarity with chemical constituents of L leptophyllum. L myrianthum revealed twelve known compounds: 3,5,7,3',4',6'-hexahydroxyflavone (10), myricetin-3-O-L-arabinoside (11), myricetin-3-O-ß-D-glucopyranoside (12), epigallocatechin-3-O-gallate (13), myricetin 3-O-(6''-galloylglucoside) (14), 3-O-(2''-O-galloyl)-ß-D-glucopyranoside (15), 1-galloyl-ß-D-glucopyranoside (16), melitriose (17), ß-sitosterol-3-glucoside (18) and ß-sitosterol (19). Compounds 11, 12, 14, 15 and 18 are reported for the first time from this plant. Myricetin (8), and myricetin-3-O-L-rhamnopyranoside (9) are present in all three species, while myricetin 3-O-(6''-galloylglucoside) (14), and 3-O-(2''-O-galloyl)-ß-D-glucopyranoside (15) were isolated only from L myrianthum and L gmelinii. In contrast to L leptophyllum and L myrianthum, L gmelinii contained quercetin-3-O-a-L-rhamnopyranoside (20) and myricetin 3-O-(4''-O-galloyl)-a-rhamnopyranoside (21), which were not found in the other investigated species. All compounds were evaluated for their antifungal, antibacterial, antileishmanial and antimalarial activities. Compound (1) showed potent activity against a chloroquine-resistant and a chloroquine-sensitive strain of malaria with IC50 values of 167.9 and 316.1 ng/mL, respectively, whereas the structurally related compound 5 showed moderate activity compared to 1 with IC50 values of 1.325 and 1.430 µg/mL, respectively. Compounds, 10, 13, 14 and 16 showed significant activities against Trypanosoma brucei with IC50 values of 7.97, 7.52, 8.32 and 8.35 µg/ml, respectively. The IC50 value for the positive drug control a-difluoromethylornithine (DFMO) was 3.88 µg/ml. Compounds 10 and 13 exhibited significant antifungal activities against Candida glabrata with IC50 values of 6.83 and 4.96 µg/ml, respectively. The IC50 value for the positive drug control, amphotericin B, was 0.28 µg/ml. Compounds 8, 11 and 15 exhibited potent cytotoxic activities against leukemia LH60 and K562 cell lines. This study resulted in the identification and isolation of medicinally and pharmacologically valuable secondary metabolites from these three Limonium species.