Chios gum mastic: A review of its biological activities.

The resin of Pistacia lentiscus (L.) var. chia (Duham), an evergreen shrub belonging to the family Anacardiaceae and uniquely cultivated in southern Chios, is known as mastic. It has been used for more than 2500 years in traditional Greek medicine for treating several diseases such as gastralgia and peptic ulcers, while the actions of the gum are mentioned in the works of Herodotus, Dioscorides and Galen. Several Roman, Byzantine, Arab and European authors make extensive references to mastic's healing properties. Modern scientific research has justified the beneficial action of mastic to gastric diseases, by revealing its in vivo and in vitro activity against Helicobacter pylori, which is considered as the main cause for gastric ulcers. Furthermore, studies of the antimicrobial, antifungal, antioxidant, hypolipidemic, anti-inflammatory, anti-Crohn and anticancer activities of mastic have characterized it as a wide-range therapeutic agent and a potential source of nature-originated treatments.

Assessment of antioxidant activity of extracts from unique Greek varieties of Leguminosae plants using in vitro assays.

BACKGROUND: It is believed that legumes are a very good source of micronutrients and phytochemicals that present chemopreventive activity against diseases such as diabetes, coronary heart disease and colon cancer. Methanolic and aqueous extracts from 11 unique varieties of Leguminosae family plants cultured in Greece were tested using three different in vitro assays in order to investigate the mechanisms by which phytochemicals present in these legumes exert their chemoprevention. MATERIALS AND METHODS: The extracts were tested by the 1, -diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, the hydroxyl radical- and the peroxyl radical-induced DNA strand scission assays. Hydroxyl (OH*) and peroxyl (ROO*) radicals were generated from ultraviolet (UV) photolysis of hydrogen peroxide (H2O2) and thermal decomposition of 2,2'-azobis-(2-amidinopropane hydrochloride) (AAPH) respectively. RESULTS: In the DPPH assay, all the tested extracts displayed potent radical scavenging efficiency. Furthermore, most of the Leguminosae family plant extracts exerted significant protective activity against DNA damage induced by both reactive oxygen species, although they were more effective in inhibiting ROO*-induced rather than OH*-induced DNA strand scission. CONCLUSION: The results suggest that the free radical scavenging activity of Leguminosae plants may be one of the mechanisms accounting for their chemoprevention.

7-Bromoindirubin-3'-oxime induces caspase-independent cell death.

Indirubin, an isomer of indigo, is a reported inhibitor of cyclin-dependent kinases (CDKs) and glycogen synthase kinase-3 (GSK-3) as well as an agonist of the aryl hydrocarbon receptor (AhR). Indirubin is the active ingredient of a traditional Chinese medicinal recipe used against chronic myelocytic leukemia. Numerous indirubin analogs have been synthesized to optimize this promising kinase inhibitor scaffold. We report here on the cellular effects of 7-bromoindirubin-3'-oxime (7BIO). In contrast to its 5-bromo- and 6-bromo- isomers, and to indirubin-3'-oxime, 7BIO has only a marginal inhibitory activity towards CDKs and GSK-3. Unexpectedly, 7BIO triggers a rapid cell death process distinct from apoptosis. 7-Bromoindirubin-3'-oxime induces the appearance of large pycnotic nuclei, without classical features of apoptosis such as chromatin condensation and nuclear fragmentation. 7-Bromoindirubin-3'-oxime-induced cell death is not accompanied by cytochrome c release neither by any measurable effector caspase activation. Furthermore, the death process is not altered either by the presence of Q-VD-OPh, a broad-spectrum caspase inhibitor, or the overexpression of Bcl-2 and Bcl-XL proteins. Neither AhR nor p53 is required during 7BIO-induced cell death. Thus, in contrast to previously described indirubins, 7BIO triggers the activation of non-apoptotic cell death, possibly through necroptosis or autophagy. Although their molecular targets remain to be identified, 7-substituted indirubins may constitute a new class of potential antitumor compounds that would retain their activity in cells refractory to apoptosis.

Olive oil and its main phenolic micronutrient (oleuropein) prevent inflammation-induced bone loss in the ovariectomised rat.

The present study was designed to evaluate the effect of olive oil and its main polyphenol (oleuropein) in ovariectomised rats with or without inflammation. Rats (6 months old) were ovariectomised or sham-operated as control. Ovariectomised rats were separated into three groups receiving different diets for 3 months: a control diet with 25 g peanut oil and 25 g rapeseed oil/kg (OVX), the control diet with 50 g olive oil/kg or the control diet with 0.15 g oleuropein/kg. The sham-operated group was given the same control diet as OVX. Inflammation was induced 3 weeks before the end of the experiment by subcutaneous injections of talc (magnesium silicate) in one-half of each group. The success of ovariectomy was verified at necropsy by the atrophy of uterine horns. Inflammation, oleuropein or olive oil intakes did not have any uterotrophic activity, as they had had no effect on uterus weight. The plasma concentration of alpha-1-acid glycoprotein (an indicator of inflammation) was increased in OVX rats with inflammation. With regard to bone variables, osteopenia in OVX was exacerbated by inflammation, as shown by a decrease in metaphyseal and total femoral mineral density. Both oleuropein and olive oil prevented this bone loss in OVX rats with inflammation. At necropsy, oleuropein and olive oil consumption had had no effect on plasma osteocalcin concentrations (marker of bone formation) or on urinary deoxypyridinoline excretion (marker of bone resorption). In conclusion, oleuropein and olive-oil feeding can prevent inflammation-induced osteopenia in OVX rats.

1-Oxo-2-hydroxy-1,2-dihydroacronycine: a useful synthon in the acronycine series for the introduction of amino substituents at 6-position and for the conversion into isopropylfuroacridones.

Thermic aromatic nucleophilic displacement of the methoxy group at C-6 of (+/-)-1-oxo-2-hydroxy-1,2-dihydroacronycine (2) by an amine is a reaction that gives a facile entry to acronycine derivatives bearing an amino substituent at this position. The introduction of the amino substituents was confirmed with a long-range 1H-15N correlation NMR spectrum at natural abundance. Under basic conditions, compound 2 can also be rearranged to the corresponding isopropylfuroacridone 12, in 80% yield.

Synthesis, cytotoxic activity, NMR study and stereochemical effects of some new pyrano[3,2-b]thioxanthen-6-ones and pyrano[2,3-c]thioxanthen-7-ones.

Some new substituted pyrano[3,2-b]thioxanthen-6-ones and pyrano[2,3-c]thioxanthen-7-ones were prepared and their cytotoxic activity was evaluated using acronycine as the reference compound. The conformation of the molecules was also investigated in an effort to correlate this parameter with the biological activity.

Volatile secondary metabolite pattern of callus cultures of Chamomilla recutita.

The effects of various plant growth regulators and culture conditions on the production of volatile secondary metabolites from callus cultures of Chamomile (Chamomilla recutita) inflorescence were investigated and the most efficient conditions were determined. The essential oil composition was assayed by GC-MS analysis and found to contain chamomillol, gossonorol, cubenol, alpha-cadinol, (-)-alpha-bisabolol, 1-azulenethanol acetate and (-)-alpha-bisabolol acetate.

Selective amination of secoiridoid glycosides to give monomeric pyridine, dimeric pyridine, and naphthyridine alkaloids.

Treatment of the secoiridoids oleuropein (4), ligstroside (5) and methyloleoside (6) by beta-D-glucosidase in the presence of ammonium chloride led exclusively to monomeric pyridine alkaloids 7, 1, and 8. Dimeric 3,4,5-trisubstituted pyridines were obtained from methyloleoside (6) when ammonium chloride was generated in the reaction mixture by successive additions of ammonia and hydrochloric acid. The use of ammonium acetate permitted conversion of secoiridoids 4 and 5 into the naphthyridine alkaloid jasminine (3).

Samioside, a new phenylethanoid glycoside with free-radical scavenging and antimicrobial activities from Phlomis samia.

A new phenylethanoid glycoside, samioside, was isolated from the aerial parts of Phlomis samia and identified as 1-O-3,4-(dihydroxyphenyl)ethyl beta-D-apiofuranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->3)-4-O-caffeoyl-beta-D-glucopyranoside (1). In addition, one known phenylethanoid glycoside and three known flavonoids were identified as acteoside (2), apigenin, chrysoeriol, and ermanin, respectively. The structure of 1 was elucidated on the basis of its spectroscopic data. Samioside (1) demonstrated scavenging properties toward the DPPH radical and antimicrobial activity against Gram-positive and -negative bacteria.

New hemisynthetic manoyl oxide derivatives with antimicrobial activity.

The synthesis and antimicrobial activity of ten labdane-type diterpenes derived from ent-3-beta-hydroxy-13-epi-manoyl oxide (ribenol) is reported. The chloroethyl carbamidic ester 9 showed the strongest antimicrobial activity against all the tested gram (+), gram (-) bacteria and pathogenic fungi. Moreover, the glycoside 11 exhibited an interesting activity against the three tested fungi.

Hydrolyzable tannins, the active constituents of three Greek Cytinus taxa against several tumor cell lines.

Hydrolyzable tannins were found to be the active cytotoxic constituents of three Greek Cytinus taxa: Cytinus ruber, Cytinus hypocistis subsp. hypocistis and Cytinus hypocistis subsp. orientalis. The cytotoxic activity was evaluated against a broad spectrum of cancer cell lines. The structure of the active compounds was investigated with NMR and electrospray-MS/MS techniques.

2,2-Dimethyl-2H-anthra[2,3-b]pyran-6,11-diones: a new class of cytotoxic compounds.

The synthesis and cytotoxic activity of some new 2,2-dimethyl-2H-anthra[2,3-b]pyran-6,11-diones is described. Certain compounds possess interesting activity against murine leukemia L-1210 cells. Relationships between the biological activity and the pyrano-ring conformations are discussed.

New semisynthetic antimicrobial labdane-type diterpenoids derived from the resin "ladano" of Cistus creticus.

The antimicrobial activity of fifteen semisynthetic labdane-type diterpenes derived from the two major natural compounds 3 and 4 of the resin "ladano" of Cistus creticus is reported. The chloroethyl carbamidic esters 15 and 20 showed the strongest antimicrobial activity against Gram(+), Gram(-) bacteria and pathogenic fungi.

Antileukemic activity of synthetic daunomycinone derivatives bearing modifications in the glycosidic moiety.

The antileukemic activities of the daunomycinone glycosides synthesized in our laboratories (compounds 4 and 7, code names S12 and S13, respectively) were characterized in L1210 cells in vitro. S13 inhibits tumor cell proliferation and viability at day 4 (IC50: 150-200 nM) more effectively than S12 (IC50: 250-450 nM), suggesting that the 4'-trifluoracetamido substitution of the glycosidic moiety of these 3'-halo daunonycinone derivatives has greater antitumor potential than the 4'-azido substitution. Since S12 and S13 do not increase but rather decrease the mitotic index of L1210 cells at 24 hours, they are not antitubulin drugs but might arrest the early stages of cell cycle progression. Pretreatments for 1.5-3 hours with S12 and S13 are sufficient to partially inhibit the rates of DNA and RNA syntheses (IC50: 4-10 microM) determined over 30- to 60-minute periods of pulse-labeling in L 1210 cells in vitro, but these daunomycinone glycosides alter neither the cellular transport of purine and pyrimidine nucleosides nor the rate of protein synthesis. After 24 hours, the concentration-dependent induction of DNA cleavage by S13 reaches a plateau at 10 microM but the weaker S12 requires 48 hours to maximally stimulate DNA cleavage like S13. The mechanism by which S13 induces DNA fragmentation is inhibited by actinomycin D, cycloheximide, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, benzyloxycarbonyl-Ile-Glu-Thr-Asp-fluoromethyl ketone, N-tosyl-L-phenylalanine chloromethyl ketone and ZnSO4, suggesting that S13 triggers apoptosis by caspase and endonuclease activation. Since microM concentrations of S12 and S13 are cytostatic and cytotoxic, but do not sufficiently inhibit RNA and protein syntheses to block their own ability to sustain the active process of apoptosis and DNA fragmentation, such 3'-halo daunomycinone glycosides might be valuable to develop new means of polychemotherapy.

Chemistry of plants from Crete: stachyspinoside, a new flavonoid glycoside and iridoids from Stachys spinosa.

The new flavonoid glycoside stachyspinoside (1), and the three iridoids, 7-O-acetyl-8-epi-loganic acid (2), ajugol (3) and harpagide (4) were isolated from Stachys spinosa. The structures of these compounds were established on the basis of mass spectrometry (ESMS and tandem MS), one- and two-dimensional nuclear magnetic resonance experiments (COSY, COSY LR, HMQC, TOCSY and HMBC) as well as simple chemical derivatization.

Homarine, a common metabolite in edible Mediterranean molluscs: occurrence, spectral data and revision of a related structure.

Homarine was isolated from nine edible species of marine molluscs belonging to classes Gastropoda, Bivalvia, and Cephalopoda. A thorough chromatographic, NMR and MS study provided evidence that homarine is a common and abundant metabolite of all these species. This study casts doubt on a previous assertion that 1,1'-dimethyl-[2,2']-bipyridinium is a metabolite of the Bivalve Callista chione.

Three new dihydroisocoumarins from the Greek endemic species Scorzonera cretica.

Extracts of the Greek endemic species Scorzonera cretica afforded three new compounds, the dihydroisocoumarin scorzocreticin (1) and its glycosides, scorzocreticoside I (2) and scorzocreticoside II (3), as well as 11 known compounds. The structures of the isolated compounds were elucidated on the basis of spectral data and chemical methods. The absolute configurations of 1-3 were established using circular dichroism.

The structure of sarcomejine: an application of long-range (1)H-(15)N correlation at natural abundance.

A new 4(1H)-quinolinone alkaloid, sarcomejine (1), has been isolated from the bark of Sarcomelicope megistophylla. Its structure has been elucidated on the basis of MS and NMR data and especially with a long-range (1)H-(15)N correlation NMR spectrum at natural abundance.

Two new alkaloids from the bark of Sarcomelicope megistophylla.

Two new alkaloids, megistophylline I (1) and megistophylline II (2), were isolated from the bark of Sarcomelicope megistophylla. Their structures have been elucidated on the basis of MS and NMR data.

Design, synthesis and biological activity of 7-O-(4-O-acetyl-3-iodo-2,3,6-trideoxy-alpha-L-arabino-hexopyranosyl) daunomycinone and 7-O-(3-chloro-2,3,6-trideoxy-4-O-propanoyl-alpha-L-lyxo- hexopyranosyl)daunomycinone.

The synthesis and pharmacological evaluation of 7-O-(4-O-acetyl-3-iodo-2,3,6-trideoxy-alpha-L-arabino-hexopyranosyl) daunomycinone and 7-O-(3-chloro-2,3,6-trideoxy-4-O-propanoyl-alpha-L-lyxo-hexopyrano syl) daunomycinone are described. Their cytotoxic activity was evaluated against normal and resistant cell lines. Both compounds exhibited activity against the adriamycin resistant cell line KB-A1. These results support the hypothesis that the increased lipophilicity of the sugar part of anthracyclines is associated with their ability to overcome multidrug resistance (MDR).