Musa H. Abu Zarga

Antiproliferative, Antimicrobial and Apoptosis Inducing Effects of Compounds Isolated from Inula viscosa

The antiproliferative and antimicrobial effects of thirteen compounds isolated from Inula viscosa (L.) were tested in this study. The antiproliferative activity was tested against three cell lines using the MTT assay. The microdilution method was used to study the antimicrobial activity against two Gram positive bacteria, two Gram negative bacteria and one fungus. The apoptotic activity was determined using a TUNEL colorimetric assay. Scanning electron microscopy was used to study the morphological changes in treated cancer cells and bacteria. Antiproliferative activity was observed in four flavonoids (nepetin, 3,3′-di-O-methylquercetin, hispidulin, and 3-O-methylquercetin). 3,3′-di-O-Methylquercetin and 3-O-methylquercetin showed selective antiproliferative activity against MCF-7 cells, with IC50 values of 10.11 and 11.23 µg/mL, respectively. Both compounds exert their antiproliferative effect by inducing apoptosis as indicted by the presence of DNA fragmentation, nuclear condensation, and formation of apoptotic bodies in treated cancer cells. The antimicrobial effect of Inula viscosa were also noticed in 3,3′-di-O-methylquercetin and 3-O-methyquercetin that inhibited Bacillus cereus at MIC of 62.5 and 125 µg/mL, respectively. Salmonella typhimurium was inhibited by both compounds at MIC of 125 µg/mL. 3,3′-di-O-Methylquercetin induced damage in bacterial cell walls and cytoplasmic membranes. Methylated quercetins isolated from Inula viscosa have improved anticancer and antimicrobial properties compared with other flavonoids and are promising as potential anticancer and antimicrobial agents.

Effects of 3,3′‐di‐O‐methylquercetin on guinea‐pig isolated smooth muscle

Abstract— The effects of the flavone 3,3′‐di‐O‐methylquercetin (DOMQ) have been examined and compared with those of quercetin, on guinea‐pig isolated ileum, trachea, and main pulmonary artery (MPA). Except for transient contractions induced by low concentrations (10−8‐3 × 10−6 M), DOMQ and quercetin (up to 3 × 10−4M) caused reduction of the tone and the phasic contractions of the ileum. A23187 reversed the inhibitory effects of quercetin but not those of DOMQ. DOMQ and quercetin caused concentration‐dependent relaxation of the trachea and the adrenaline‐contracted MPA. DOMQ shifted to the right the concentration‐effect curves induced by acetylcholine on the ileum and the trachea, and by adrenaline on MPA and those induced by CaCl2 on ileum, trachea and MPA. DOMQ also inhibited the contractions induced, in Ca2+‐free EGTA‐containing buffer, by histamine on ileum and by adrenaline on MPA. These observations suggest that DOMQ inhibits Ca2+ influx, Ca2+ release from intracellular stores and, more likely, Ca2+ binding to intracellular receptor proteins.

The quettamines: a new class of isoquinoline alkaloids

Three quettamine type alkaloids, which incorporate either a benzofuran or a dihydrobenzofuran moiety within the molecular framework, have been obtained from Berberis baluchistanica. These are dihydrosecoquettamine (1), secoquettamine (2), and quettamine chloride (3). Alkaloids 1 and 3 are racemates. Hofmann degradation of quettamine (3) provides secoquettamine (2) and the styrene 4 which has a trans relationship between the hydrogens at C-1 and C-α, thus indicating the identical stereochemistry in quettamine. Emde reduction of quettamine leads to dihydrosecoquettamine (1) and the stilbene 5. Two other polar alkaloids in the plant are (+)-armepavine methochloride (6) and oblongine chloride (7). An oblongine type alkaloid must be the biogenetic precursor for the quettamines. Arguments are presented favoring direct oxidative coupling in the biogenesis of the cularine alkaloids.

A New Eudesmane Type Sesquiterpene from Inula Viscosa

Investigation of Inula viscosa of Jordanian origin afforded the new sesquiterpene 1 g -hydroxyilicic acid in addition to the known 2 g -hydroxyilicic acid.

The absolute configuration of berberastine and thalidastine

Abstract Optical resolution of (±)-tetrahydrojatrorrhizine using (-)-O,O-di- p -toluoyl- d -tartaric acid gave rise to (+)-tetrahydrojatrorrhizine ( 6 of high optical purity and of known absolute configuration. Oxidation of this enantiomer with lead tetraacetate, followed by acid hydrolysis, furnished alcohols 10 and 11 in a 2:1 ratio, whose relative stereochemistry was established from their nmr spectra. Iodine oxidation of the major alcohol 10 led to protoberberinium salt 14 which was found to be dextrorotatory. Since berberastine ( 1 ) and thalidastine ( 2 ) are also dextrorotatory, they must possess the same absolute configuration as 14 .

A lupine alkaloid from Leontice leontopetalum

Abstract Leontice leontopetalum from Jordan has yielded the new lupine alkaloid, 3α-hydroxylupanine. Its structure was confirmed by the use of mono- and bi-dimensional NMR techniques (GASPE, DEPT, homonuclear spindecoupling experiments, 1 H/ 1 H-COSY, 1 H/ 13 C-COSY), linked scan measurements and by chemical transformation. The isolation of 13α-hydroxylupanine and isolupanine are also described and their 1 H and 13 C NMR spectral data have been reinvestigated employing GASPE, DEPT, HMQC and HOHAHA experiments.

Phenolics from Colchicum decaisnei

Abstract Colchicum decaisnei has yielded three new compounds, namely, dibenzo[ b , f ][1,5]dioxocin, 4,6-dimethoxy-3,7-dimethyl coumarin and 3- O -demethyl- N -desacetyl- N -formyl-β-lumicolchicine, as well as the first report of 2-hydroxy-3-methoxy benzoic acid from a natural source.

Fumadensine a phthalideisoquinoline from Fumaria densiflora

Abstract The new phthalideisoqunoline, fumadensine, has been isolated from extracts of Fumaria densiflora .

Three new seco-ursadiene triterpenoids from Salvia syriaca.

Three new seco-ursadiene triterpenoids 1–3 together with 11 known compounds were isolated from Salvia syriaca of Jordanian origin. The compounds were identified by using NMR spectroscopy including extensive 2D NMR experiments and mass spectrometry. The structure of compound 3 was confirmed by X-ray crystallography, and the information thus obtained was used to confirm the stereochemistry of compounds 1 and 2. This is the second report of 17,22-seco-17(28),12-ursadien-22-oic acids.

Chemical constituents of Osyris alba and their antiparasitic activities

Phytochemical investigation of Osyris alba L. (Santalaceae) of Jordanian origin resulted in the isolation and identification of one new pyrrolizidine alkaloid, osyrisine (1), together with 16 other known compounds. The structures of all compounds were established on the basis of spectroscopic analysis. Osyrisine, catechin, and catechin-3-O-α-l-rhamnopyranoside exhibited a significant level of antiparasitic activity against two parasites, Entamoeba histolytica and Giardia intestinalis.