Haloxylines A and B, Antifungal and Cholinesterase Inhibiting Piperidine Alkaloids from <i>Haloxylon salicornicum</i>

Abstract

Haloxylon salicornicum (MOQ.-TAND.) Boiss belongs to the family Chenopodiaceae which comprises 100 genera and 1200 species. Most of the members of this family are weedy and grow in waste and unfertile areas of soil. In Pakistan, this family is represented by 35 genera. Only five species of genus Haloxylon are found in Pakistan. Haloxylon salicornicum is a diffuse shrub, pale, much branched, almost leafless, 25-60 cm tall, with woody stem. It is widely distributed in Egypt, Palestine, Jordan, Iraq, Kuwait, Iran, and Pakistan.1) The plant is traditionally reported for its toxicity and applied externally on insect stings.2) The ash of the plant is used for internal ulcers.3) Three alkaloids and a pyranone derivative have so far been reported from this species. [4][5][6] A methanolic extract of this plant showed strong cytotoxicity in brine shrimp lethality test. 7) On further fractionation, the major cytotoxicity was detected in the chloroform-soluble fraction. Further pharmacological screening of this fraction revealed strong antifungal and cholinesterase inhibiting activities. This prompted us to carry out bioassay-guided isolation of bioactive compounds from the chloroform-soluble fraction. As a result of these studies we have isolated two new piperidine alkaloids named as haloxylines A (1) and B (2). Both 1 and 2 showed antifungal and cholinesterase inhibiting activities. Results and DiscussionThe methanolic extract of the whole plant of H. salicornicum was processed as described in Experimental to afford new piperidine alkaloids named as haloxylines A (1) and B (2). Haloxyline A (1) was isolated as colorless crystals (14 mg). The high-resolution (HR) EI-MS of (1) showed the molecular ion peak at m/z 419.3749 (Calcd for C 27 H 49 NO 2 , 419.3763) possessing four degrees of unsaturation. The IR spectrum of 1 showed an amide carbonyl at 1640 cm Ϫ1 and conjugated double bonds at 1620 cm (C-4). All the assignments were confirmed by hetronuclear multiple quantum coherence (HMQC). The cumulative evidences allowed us to assign the structure of haloxyline A (1) as (Z,Z)-1-(22-hydroxy-1-oxo-2,4-docosadienyl) piperidine. The heteronuclear multiple-bond correlations (HMBC) were in exact agreement to the assigned structure.Haloxyline B (2) was also obtained as colorless crystals (12 mg). The molecular formula was established by HR-EI-MS showing molecular ion peak at m/z 435.3701 (Calcd for C 27 H 49 NO 3 , 435.3712) with four degrees of unsaturation. The UV and IR spectrum were almost superimposable to those of 1. The presence of hydroxy substituted piperidine ring was revealed by peaks in EI-MS and HR-EI-MS at m/z 100 and 100.0058 respectively. Therefore, haloxyline B (2) differs from (1) in having additional alcoholic group in the piperidine ring. In 1 H-NMR spectrum the signals of piperidine differed from those of 1. The hydroxymethine proton * To whom correspondence should be addressed. Haloxylines A (1) and B (2), new piperidine alkaloids, have been isolated from the chloroform soluble fraction of Haloxylon salicorni...

The Biological Activity of Natural Alkaloids against Herbivores, Cancerous Cells and Pathogens

“…Another alkaloid, 6,8-didec-(1Z)-enyl-5,7-dimethyl-2,3-dihydro-1H-indolizinium ( 64 in Figure 10) was isolated from Anibapanurensis and demonstrated excellent activity against the strain of C. albicans [180].…”

HPLC-Based Activity Profiling for GABAA Receptor Modulators: A New Dihydroisocoumarin from Haloxylon scoparium

“…Table 1. 1 H, 13 C, and 2D-NMR Data (d-Chloroform) of (S)-4-Methoxy-7-phenyl-7,8-dihydro [1,3] Microfractionation. Microfractionation for GABA A receptor activity profiling was performed as previously described, 7 with minor modifications: Separation was carried out on a semipreparative HPLC column with acetonitrile (solvent A) and water (solvent B) using the following gradient: 5% A for 7 min, 5% A to 100% A over 38 min, 100% A for 8 min.…”

“…H. scoparium is a small, highly branched halophytic shrub distributed in sandy waste places of North Africa and the Middle East. Haloxylon species contain numerous alkaloids, − sterols, , flavonoid glycosides, and pyranones, for which cholinesterase and chymotrypsin inhibitory, antifungal, and nicotinergic activities have been described. We here report on a new dihydroisocoumarin ( 1 ) acting as a positive allosteric modulator of the GABA A receptor.…”

“…Supporting Information Available: 1 H NMR, 13 C NMR, 1 H-1 H COSY, NOESY, HSQC, HMBC, and CD spectra of 1 are available free of charge via the Internet at http://pubs.acs.org.…”

Using the secondary metabolites of some fungi and wild plants as natural pesticides to control cotton mealybug, Phenacoccus solenopsis (Hemiptera: Pseudococcidae)

“…Halexylon salicornicum (the old scientific name was Hammad elegans) is a wild plant that belongs to the family Chenopdiaceae and contains mainly alkaloids such as anabasine, betine, piperidine, aldotripiperideine, haloxine, haloxyline A and B (Ferheen et al 2005). Anabasine has insecticidal activity against lepidopterous larvae (Pieris rapae) at low concentrations, as mentioned by Zammit et al (2014).…”