Four new and 14 known compounds have been isolated from Inula viscosa of Jordanian origin. The new isolates are 11(13)-eudesmen-12-oic acids, 3beta-hydroxyilicic acid (1), 3alpha-hydroxy-epi-ilicic acid (2), 2alpha-hydroxyilicic acid (3) and 9beta-hydroxy-2-oxoisocostic acid (4).

A [1] and B [2], have been isolated from the aerial parts of Ziziphus lotus, together with the known alkaloids sanjoinenine [3], sanjoinine F [4], and frangufoline [51• Ziziphus lotus Lam. (Rhamnaceae) is a small tree that is widely distributed in the Jordan Valley. The genus Ziziphus comprises several species that are used in indigenous medicine for the treatment of various diseases (1-5). We report here the first chemical investigations of Z. lotus, yielding two new 14-membered frangulanine-type (6) cyclopeptide alkaloids from an extract of the aerial pans of Z. lotus. The new compounds, lotusanine A [1} and lotusanine B [2] were isolated along with the known alkaloids, sanjoinenine {31 (7), sanjoinine F [4] (7), and frangufoline [51 (8) (Table 1). Characterization of these compounds was achieved with the help of spectroscopic studies, especially mass spectrometry, which permitted conclusions to be drawn about the structural units (amino acids and styryl moiety) present in the compound and the manner in which they are linked (6,9). RESULTS AND DISCUSSIONCc of an alkaloidal fraction of the C6H6 extract of Z. lotus (see Experimental) gave an amorphous solid, lotusanine A [1]. The uv spectrum of 1 showed only terminal absorption. The ir spectrum exhibited bands for NH-(3260 cm '), amide carbonyls

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Haplophyllum buxbaumii has yielded three new lignan type A glucosides: majidine [2], qudsine [3], and arabelline [4], Cleistanthin B [1] is also reported for the first time from this family. Temperature-dependent nmr studies have provided insight into the conformational equilibria existing in 1, 2, and 4.In continuation of our systematic phytochemical investigation of Haplophyllum buxbaumii A. Juss. (Rutaceae) (1), we now report the isolation and structure elucidation of four diphyllin glucosides, three of which (2-4) are new. These are cleistanthin B [1], 4-The bluish fluorescence of the four lignan glucosides under uv light as well as their similar uv spectra (X max 261.6 nm) indicated that all these compounds bear an arylnaphthalene nucleus (2). The acid hydrolysis of the four lignan glucosides afforded the same aglycone, which was identified by spectral data as diphyllin [11] (12). The sugar residues, identified by tic comparison with authentic samples, were found to be glucose of compound 1, apiose and xylose of compound 2, apiose, arabinose, and glucose of compound 3, and arabinose and glucose of compound 4.The uv, ir, ms, and 'H-nmr spectra were reported for cleistanthin B (3). As the 'Hnmr assignments were not fully made, we present in Table 1 the 'H-nmr spectrum with the assignments of the individual aromatic protons. The 13C-nmr chemical shifts and multiplicity assignments of cleistanthin B are shown in Table 2.Compound 2 was assigned the molecular formula C31H32015) positive fabms m!z 645 [M + H]+). The 'H-nmr spectrum of the acetylated derivative 6 of compound 2showed five 3 H singlets in the region between 2.02 and 2.14, corresponding to the aliphatic acetoxy groups, indicating the presence of five aliphatic hydroxyl groups. The 13C-nmr spectrum (DMSO-

Background/Aims: In our quest to develop an isoindigo with improved efficacy and bioavailability, we recently synthesized a series of novel substituted pyridone-annelated isoindigo and evaluated their antiproliferative effects. We identified the compound [(E)-1-(5'-Chloro-2'-oxoindolin-3'-ylidene)-6-ethyl-2,3,6,9-tetrahydro-2,9-dioxo-1H-pyrrolo[3,2-f] quinoline-8-carboxylic acid], abbreviated as 5'-Cl, which shows selective antiproliferative activities against various cancer cell lines mediated through apoptosis. Here we have investigated the molecular mechanisms underlying the apoptotic activity of 5'-Cl in the human promyelocytic leukemia HL-60 cells. Methods: We employed different methods to determine the apoptotic pathways triggered by 5'-Cl in HL-60 cells, using flow cytometry, nuclear staining, caspases activation, mitochondria functioning, generation of reactive oxygen species (ROS) and Western blotting techniques. Results: Low concentrations (1-8 µM) of 5'-Cl inhibited the growth of HL-60 cells in a dose and time-dependent manner. Cytotoxicity of this compound is found to be mediated by a caspase-dependent apoptosis. Also, there were indications of caspase independent apoptosis as z-VAD-FMK failed to fully rescue the cells from 5‘-Cl-induced apoptosis. In addition, the compound triggered generation of Reactive Oxygen Species (ROS), caused depolarization of the mitochondrial inner membrane, decreased the level of cellular ATP, modulated the expression and phosphorylation of Bcl-2 leading to loss of its association with Bax and increased the release of cytochrome c to the cytosol of treated cells. The effects of 5‘-Cl on mitochondria and apoptosis were substantially blocked in the presence of a combination between z-VAD-FMK and either of the ROS scavenger N-acetyl-L-cysteine (NAC) or pyrrolidine dithiocarbamate (PDTC). Conclusion: We demonstrated that the growth inhibitory effects of 5'-Cl in HL-60 cells involve multiple pathways of apoptosis and dysregulation of mitochondrial functions.

Phytochemical analysis of the ground aerial parts of Artemisia arborescens resulted in the isolation from the ethanolic extract of the known compounds: artemitin, arborescin, sesamin, (+)-lirioresinol beta-dimethyl ether, chrysoeriol, apigenin, beta-sitosteryl glucoside, dihydroridentin, and chrysoeriol 4-glucoside. The last six compounds are isolated from this plant for the first time. The same fraction also yielded the new eudesmanolide jordanolide (1). The effect of an aqueous extract of the plant was studied on rat isolated ileum, uterus, and urinary bladder. The aqueous extract (AE) caused a concentration-dependent reduction in the amplitude of the phasic contractions and in the tone of the ileum. On the other hand, AE caused a significant increase in the frequency as well as the amplitude of the phasic contractions and increased the tone of the isolated uterus and the urinary bladder strips. On the uterus, quinacrine, an inhibitor of the release of arachidonic acid and its metabolites, and indomethacin, a cyclooxygenase inhibitor, potentiated rather than inhibited the effects of AE on this tissue. These observations are discussed in relation to the use of the plant extract in folk medicine.

Colchicum ritchii of Jordanian origin has yielded the three non-nitrogenous colchicinoids colchicone [1], 3-demethylcolchicone [2], and comigerone [3], as well as the amidic (-)-colchibiphenyline, which in CDClj solution exists as a mixture of isomers 4a and 4b. Ketones 1-3 may exemplify one catabolic route for the colchicine alkaloids, while (-)-colchibiphenyline [4a,4b], and the accompanying and previously known (-)-androbiphenyline [5a,5b] may exemplify another.Five Colchicum species (Liliaceae) are native to Jordan. These are Colchicum crocifolium Boiss., Colchicum decaisnei Boiss., Colchicum triphyllum G. Kuntze, Colchicum steveni Kunth, and Colchicum ritchii R. Br. (1). The last of these, namely C. ritchii, has been the subject of an investigation that has revealed the presence of a number of diphenolic phenethyltetrahydroisoquinoline-, androcymbine-, and colchicine-type alkaloids (2).The present study was focused on the acid-insoluble components of C. ritchii. Extensive chromatography of the acid-insoluble extracts furnished three closely related ketonic and non-nitrogenous compounds, which also incorporate a tropolone system.The first of these, colchicone [1], C20H20O6, had a mass spectrum showing a molecular ion peak m!z 356 (54%) and base peak mtz 328 [M -CO]+. The presence of two carbonyls was indicated by the ir spectrum, which included a strong band at 1610 cm-1 for the tropolonic carbonyl and another at 1710 cm-1 for the ketonic group of ring B.The existence of these two carbonyls was confirmed by the 13C-nmr spectrum, which displayed downfield singlets for the carbonyl carbons at 179 37 (ring C) and at 205.66 (ring B).Extensive 1H-nmr spin decoupling and nOe experiments resulted in the detailed 'H-nmr values summarized around structure 1. Four methoxyl singlets were in evidence with the most upfield, at 3.55, assigned to the highly hindered 1-OMe, while the most downfield, at 4.00, represented the tropolonic 10-OMe. It was even possible to differentiate between the two remaining methoxyl singlets at 3.86 and 3.87, with the former due to 2-OMe and the latter to 3-OMe. Four aromatic proton signals, two appearing as two singlets and the two others as two doudsgem '3.7

Investigation of Capparis spinosa of Jordanian origin lead to isolation of two new compounds beta-sitosterylglucoside-6'-octadecanoate (1) and 3-methyl-2-butenyl-beta-glucoside (2). Linked Scan MS measurements were used to propose a mass fragmentation pattern for the alkaloid Cadabicine isolated here for the second time from nature.