trispheridine and lycorine

Plants of the Zephyranthes genus are globally used in folk medicine. In a previous study, Zephyranthes candida Linn. (Amaryllidaceae) was identified as having antiviral properties; this led to anti-poliovirus assay-guided isolation of compounds from crude methanol extract of the plant.. Isolation of anti-poliovirus constituents from Z. candida.. Active chloroform fraction from crude methanol extract of Z. candida (whole plant) was subjected to bioassay-guided fractionation; repeated column and preparative thin layer chromatography led to isolation of active compounds. Chemical structures were identified using spectroscopic techniques. Using serial two-fold dilution of maximum non-toxic concentration (MNTC) of each compound (0.0625-1 µg/mL for lycorine and 0.625-10 µg/mL for trisphaeridine and 7-hydroxy-3',4'-methylenedioxyflavan), the ability of extracts to inhibit viral-induced cell death in tissue culture was evaluated 72 h post-infection by the colorimetric method using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) dye. Regression analysis was used to determine 50% inhibitory concentration (IC50) and 50% cytotoxicity concentration (CC50), from which selective index (SI) was calculated.. From the chloroform fraction, three compounds were isolated and identified, namely lycorine (1), trisphaeridine (2), and 7-hydroxy-3',4'-methylenedioxyflavan (3) as the anti-polioviral components. Lycorine was the most active, with an IC50 value of 0.058 µg/mL followed by trisphaeridine (2) with an IC50 of 0.1427 µg/mL, and 7-hydroxy-3',4'-methylenedioxyflavan (3) with an IC50 of 0.2384 µg/mL.. The antipoliovirus activity of trisphaeridine (2) and 7-hydroxy-3',4'-methylenedioxyflavan (3) is established in this report; these compounds are of moderate toxicity and have very good SI. They could be a potential template for the development of a new antiviral agent.

Topics: Alkaloids; Amaryllidaceae Alkaloids; Antiviral Agents; Cell Line; Cell Survival; Cytopathogenic Effect, Viral; Dioxoles; Humans; Inhibitory Concentration 50; Liliaceae; Phenanthridines; Plant Extracts; Poliovirus

Seven new alkaloids, N-methylhemeanthidine chloride (1), N-methyl-5,6-dihydroplicane (5), O-methylnerinine (6), N-ethoxycarbonylethylcrinasiadine (7), N-ethoxycarbonylpropylcrinasiadine (8), N-phenethylcrinasiadine (9), and N-isopentylcrinasiadine (10), together with eight known alkaloids, hemeanthamin (2), 3-epimacronine (3), (+)-tazettine (4), N-methylcrinasiadine (11), trisphaeridine (12), 5,6-dihydrobicolorine (13), lycorine (14), and nigragillin (15), were isolated from the whole plants of Zephyranthes candida. The structures of the new compounds were established by spectroscopic data interpretation, with single-crystal X-ray diffraction analysis performed on 1. The absolute configuration of 3-epimacronine (3) was determined by single-crystal X-ray diffraction analysis with Cu Kα irradiation. Compounds 1-15 were evaluated for their in vitro cytotoxicity against five human cancer cell lines and the Beas-2B immortalized (noncancerous) human bronchial epithelial cell line. Compounds 1, 2, 9, and 14 exhibited cytotoxicity with IC(50) values ranging from 0.81 to 13 μM with selectivity indices as high as 10 when compared to the Beas-2B cell line.

Topics: Amaryllidaceae Alkaloids; Antineoplastic Agents, Phytogenic; Crystallography, X-Ray; Dioxoles; Drug Screening Assays, Antitumor; Drugs, Chinese Herbal; Humans; Liliaceae; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Phenanthridines

To study the chemical constituents from the bulbs of Zephyranthes candida.. The chemical constituents were separated and purified by means of several chromatographies and their structures were elucidated by spectroscopic methods.. Six compounds were isolated and identified as trisphaeridine (I), p-hydroxybenzaldehyde (II), sucrose (III), (-)-amarbellisine (IV), lycorine (V), (+)-haemanthamine (VI).. Compounds I - IV are obtained from this genus for the first time.

Topics: Amaryllidaceae Alkaloids; Benzaldehydes; Dioxoles; Ethanol; Liliaceae; Magnetic Resonance Spectroscopy; Phenanthridines; Plant Roots; Sucrose

The 80% aqueous methanolic extract from the bulbs of Crinum yemense showed a potent inhibitory effect on nitric oxide production in lipopolysaccharide-activated macrophages. Three new crinine-type alkaloids, yemenines A (1), B (2), and C (3), were isolated from the herbal extract together with six known alkaloids. The absolute configurations of 1-3 were determined on the basis of chemical and physicochemical evidence. The effects of the isolated alkaloids on nitric oxide production in lipopolysaccharide-activated macrophages were examined, and several alkaloids, e.g. 1, (+)-bulbispermine (6), (+)-crinamine (7), (+)-6-hydroxycrinamine (8), and (-)-lycorine (9), showed inhibitory effects on nitric oxide production and induction of inducible nitric oxide synthase.

Topics: Alkaloids; Amaryllidaceae Alkaloids; Crinum; Enzyme Inhibitors; Indolizines; Lipopolysaccharides; Macrophages, Peritoneal; Molecular Structure; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Phenanthridines; Plants, Medicinal; Yemen

Seven alkaloids were isolated from Sprekelia formosissima, and five from Hymenocallis x festalis. Tazettine, lycorine, haemanthidine and haemanthamine were evaluated for antiproliferative and multidrug resistance (mdr) reversing activity on mouse lymphoma cells. Lycorine, haemanthidine and haemanthamine displayed pronounced cell growth inhibitory activities against both drug-sensitive and drug-resistant cell lines, but did not significantly inhibit mdr-1 p-glycoprotein. Thus, the tested alkaloids are apparently not substrates for the mdr efflux pump. Assays for interactions with DNA and RNA revealed that the antiproliferative effects of lycorine and haemanthamine result from their complex formation with RNA.

Topics: Alkaloids; Amaryllidaceae Alkaloids; Aniline Compounds; Animals; Antineoplastic Agents, Phytogenic; Dioxoles; DNA; Drug Resistance, Multiple; Leukemia L5178; Magnoliopsida; Mice; Molecular Structure; Nucleic Acid Denaturation; Phenanthridines; Plant Stems; RNA, Transfer; Tumor Cells, Cultured; Verapamil