Standardization of homeopathic <Emphasis Type="Italic">Coffea arabica</Emphasis> (<Emphasis Type="Italic">Coffea cruda</Emphasis>) and <Emphasis Type="Italic">Coffea tosta</Emphasis> matrix tinctures

Methods of standardization and quality control of homeopathic matrix tinctures of Coffea arabica and Coffea tosta obtained using green and roasted coffee beans are described. They include the organoleptic characteristics, qualitative reactions, TLC, quantitative estimation of caffeine and total phenolcarboxylic acids (calculated as caffeic acid), relative density, and percentage of dry residue. The period of expiration on storage is established at two years. These methods are included in drafts of pharmacopoeial monographs for homeopathic matrix tinctures of Coffea arabica and Coffea tosta. Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 42, No. 11, pp. 45–48, November, 2008.     

Novel cycloartane-type triterpenoid from the fruits of <Emphasis Type="Italic">Nandina</Emphasis><Emphasis Type="Italic">domestica</Emphasis>

A novel cycloartane-type triterpenoid was isolated from the fruits of Nandina domestica (Berberidaceae). The structure was characterized as 24-methylene-3-oxocycloartane 13-carboxylic acid on the basis of NMR spectroscopic data.     

Antileishmanial amides and lignans from <Emphasis Type="Italic">Piper cubeba</Emphasis> and <Emphasis Type="Italic">Piper retrofractum</Emphasis>

The n-hexane, ethyl acetate, methanol, and acetone extracts of Piper cubeba Linn. and P. retrofractum Vahl. (Piperaceae) were evaluated in vitro against promastigotes of Leishmania donovani, and all exhibited significant in vitro activity at 100 μg/ml. Two lignans, cubebin and hinokinin, were isolated from the hexane extract of P. cubeba; and one bis-epoxy lignan, (−)-sesamin, and two amides, pellitorine and piplartine, were isolated from the hexane and methanol extracts of P. retrofractum. Cubebin and piplartine showed significant antileishmanial activity in vitro at 100 μM and were further tested in vivo in a hamster model of visceral leishmaniasis. Piplartine showed activity at 30 mg/kg dose. This is the first report of antileishmanial activity of these two plants and their isolated constituents. NIPER Communication No. 395.     

Secoiridoid glycosides from the leaves of <Emphasis Type="Italic">Hydrangea macrophylla</Emphasis> subsp. <Emphasis Type="Italic">serrata</Emphasis>

Seven secoiridoid glycosides, secologanin dimethyl acetal (1), n-butyl vogeloside (2), n-butyl epi-vogeloside (3), (7R)-n-butyl morroniside (4), hydrangenoside A (5), hydrangenoside C (6), and hydrangenoside A dimethyl acetal (7), have been isolated from the leaves of Hydrangea macrophylla subsp. serrata (Thunb.) Makino (Saxifragaceae). The structures were elucidated on the basis of spectral data.     

Synthesis and antimicrobial activity of 1<Emphasis Type="Italic">H</Emphasis>,10<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">e</Emphasis>]pyrrolo[3,2-g]indole derivatives

We have synthesized a series of new phenylazo derivatives of 1H,10H-benzo[e]pyrrolo[3, 2-g]indole containing 3-(p-bromophenylazo) (II), 3-(p-iodophenylazo) (III), 3-(p-sulfamidophenylazo) (IV), 3-formyl (V), 3,8-diformyl (VI), 3-phenylazo (VII), 3-(p-chlorophenylazo) (VIII), 3-(p-nitrophenylazo) (IX), 2,9-di(adamantylaminocarbonyl) (X), 2,9-di(p-benzenesulfamidoaminocarbonyl) (XI), 2,9-di(isonicotinoylhydrazidecarbonyl) (XII), and 2,9-di(carbohydrazide) (XIII) substituents. The antimicrobial, antifungal, and antituberculosis activity was investigated in vitro with respect to various microorganisms including conditionally pathogenic mycobacteria and pathogenic fungi. It is established that the tested compounds possess high antimicrobial activity. The synthesized compounds are of great interest for further, more thorough investigations and experiments on animals with the corresponding infectious diseases. Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 43, No. 2, pp. 23–25, February, 2009.     

Influence of chloride on the chronic toxicity of sodium nitrate to <Emphasis Type="Italic">Ceriodaphnia dubia</Emphasis> and <Emphasis Type="Italic">Hyalella azteca</Emphasis>

While it has been well established that increasing chloride concentration in water reduces the toxicity of nitrite to freshwater species, little work has been done to investigate the effect of chloride on nitrate toxicity. We conducted acute and chronic nitrate (as sodium nitrate) toxicity tests with the cladoceran Ceriodaphnia dubia and the amphipod Hyalella azteca (chronic tests only) over a range of chloride concentrations spanning natural chloride levels found in surface waters representative of watersheds of the Great Lakes Region. Chronic nitrate toxicity test results with both crustaceans were variable, with H. azteca appearing to be one of the more sensitive invertebrate species tested and C. dubia being less sensitive. While the variability in results for H. azteca were to an extent related to chloride concentration in test water that was distinctly not the case for C. dubia. We concluded that the chloride dependent toxicity of nitrate is not universal among freshwater crustaceans. An additional sodium chloride chronic toxicity test with the US Lab strain of H. azteca in the present study suggested that when present as predominantly sodium chloride and with relatively low concentrations of other ions, there is a narrow range of chloride concentrations over which this strain is most fit, and within which toxicity test data are reliable.     

Polygosumic acid,a new cadinane sesquiterpene from <Emphasis Type="Italic">Polygonum viscosum</Emphasis>, inhibits the growth of drug-resistant <Emphasis Type="Italic">Escherichia coli</Emphasis> and <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> (MRSA) in vitro

Three new sesquiterpenes, 6-hydroxy-7-(1-methylethyl)-3,3a,6,7,8,8a-hexahydroazulene-1,4-dicarboxylic acid methyl ester (1, named viscozulenic acid methyl ester), 7-(1-methylethyl)-3,3a,6,7,8,8a-hexahydroazulene-1,4-dicarboxylic acid 1-methyl ester (2, named viscoazucinic acid) and 3-oxo-1-epi-sclerosporin (3, named polygosumic acid), have been isolated from the chloroform extract of the aerial parts of Polygonum viscosum by reversed-phase preparative high performance liquid chromatography (HPLC). The structures of these compounds were established conclusively by ultraviolet (UV), mass spectrometry (MS) and a series of 1D and 2D nuclear magnetic resonance (NMR) analyses. The anti-bacterial properties of 1–3 against 12 pathogenic bacterial strains have also been assessed by the rapid and robust microtitre-plate-based serial dilution method incorporating resazurin as an indicator of cell growth. Polygosumic acid was the most active among the sesquiterpenes and inhibited the growth of penicillin-resistant Escherichia coli (minimum inhibitory concentration, MIC=0.05 mg/ml) and methicillin-resistant Staphylococcus aureus (MRSA) (MIC=0.10 mg/ml).     

Chemical studies on monoterpenoid indole alkaloids from medicinal plant resources <Emphasis Type="Italic">Gelsemium</Emphasis> and <Emphasis Type="Italic">Ophiorrhiza</Emphasis>

We have proved that the plant of origin of “Yakatsu”, one of the ancient medicines stored in Shosoin Repository, is Gelsemium elegans (Loganiaceae). Exhaustive investigation of the alkaloids in this plant as well as its closely related plant, G. sempervirens, resulted in the isolation of more than 50 compounds, including new gelsedine-, sarpagine-, and yohimbane-type alkaloids. Pharmacological study of representative and new Gelsemium alkaloids revealed that the gelsedine-type alkaloids exhibit potent cytotoxic activity against the A431 human epidermoid carcinoma cell line. It was found that Ophiorrhiza pumila (Rubiaceae) produces a remarkable anti-tumor alkaloid, camptothecin, and its related alkaloids, including new compounds that might be the biogenetic precursors of camptothecin. Chemical investigation of callus cultures, regenerated plants, and hairy roots of O. pumila revealed that the regenerated plants and the hairy roots produce almost the same alkaloids, including camptothecin, as do the wild-type plants.     

(<Emphasis Type="Italic">Z</Emphasis>)-3-Hexenyl diglycosides from <Emphasis Type="Italic">Spermacoce laevis</Emphasis> Roxb.

A new (Z)-3-hexenyl O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside was isolated from the aerial part of Spermacoce laevis, along with 17 known compounds: (6S,9R)-roseoside, (Z)-3-hexenyl O-β-d-glucopyranoside, (Z)-3-hexenyl O-α-l-rhamnopyranosyl-(1→6)-β-d-glucopyranoside, (Z)-3-hexenyl O-α-l-arabinopyranosyl-(1→6)-β-d-glucopyranoside, phenyethyl O-β-d-glucopyranoside, phenyethyl O-α-l-arabinopyranosyl-(1→6)-β-d-glucopyranoside, phenyethyl O-α-l-rhamnopyranosyl-(1→6)-β-d-glucopyranoside, benzyl O-α-l-arabinopyranosyl-(1→6)-β-d-glucopyranoside, benzyl O-β-d-xylopyranosyl-(1→6)-β-d-glucopyranoside, asperuloside, 6α-hydroxyadoxoside, asperulosidic acid, kaempferol 3-O-β-d-glucopyranoside, kaempferol 3-O-rutinoside, quercetin 3-O-β-d-galactopyranoside, quercetin 3-O-α-l-rhamnopyranosyl-(1→6)-β-d-galactopyranoside, and rutin. The structure determinations were based on physical data and spectroscopic evidence.     

Two novel A-<Emphasis Type="Italic">seco</Emphasis>-rearranged lanostane triterpenoids from <Emphasis Type="Italic">Abies sachalinensis</Emphasis>

Further chemical study led to two new A-seco-rearranged lanostane triterpenoid derivatives (1–2) and one known compound Abiesanolide C (3) from the ethyl acetate (EtOAc) soluble fraction of the MeOH extract of Abies sachalinensis needles. The new compounds were identified as 3,4-seco-8-(14→13R)abeo-17,13-friedo-9β-lanosta-4(28), 7, 14, 24-tetraen-26,23-olide-23-hydroxy-3-oic acid and methyl-3,4-seco-8-(14→13R) abeo-17,13-friedo-9β-lanosta-4(28), 7, 14, 24-tetraen-26,23-olide-23-hydroxy-3-oate, respectively. Structural determination of these compounds were carried out by the spectral studies especially by the two digital (2D)-NMR and high-resolution (HR)-MS experiences.     

<Emphasis Type="Italic">In-Silico</Emphasis> Approaches to Multi-target Drug Discovery

Multi-target drugs against selective multiple targets improve therapeutic efficacy, safety and resistance profiles by collective regulations of a primary therapeutic target together with compensatory elements and resistance activities. Efforts have been made to employ in-silico methods for facilitating the search and design of selective multi-target agents. These methods have shown promising potential in facilitating drug discovery directed at selective multiple targets.     

Total synthesis and full NMR assignment of ourouparine,a yohimbane-type indole alkaloid isolated from <Emphasis Type="Italic">Gelsemium</Emphasis><Emphasis Type="Italic">sempervirens</Emphasis>

A yohimbane-type indole alkaloid, ourouparine, was found in Gelsemium sempervirens, and its structure was elucidated by spectroscopic analysis and total synthesis.     

Phenethyl Isothiocyanate Sensitizes Androgen-Independent Human Prostate Cancer Cells to Docetaxel-Induced Apoptosis <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis>

Purpose  

The present study was undertaken to determine efficacy of phenethyl isothiocyanate (PEITC) for sensitization of androgen-independent human prostate cancer cells (AIPC) to Docetaxel-induced apoptosis using cellular and xenograft models.     

Studies of the chemical constituents of the flower buds of <Emphasis Type="Italic">Magnolia kobus</Emphasis> and <Emphasis Type="Italic">M. salicifolia</Emphasis>

The constituents of the flower buds of Magnolia kobus DC. and M. salicifolia MAXIM. have been investigated. We isolated and identified six bis-tetrahydrofuran-type and three tetrahydrofuran-type lignan derivatives from M. kobus, and one bis-tetrahydrofuran-type lignan and eight phenylpropanoid-type derivatives from M. salicifolia. The structures of these compounds were elucidated on the basis of chemical and spectroscopic evidence.     

Bioenergetic effects of sodium sulfate on the freshwater crustacean, <Emphasis Type="Italic">Ceriodaphnia dubia</Emphasis>

I tested the hypothesis that if sodium sulfate alters the bioenergetics of Ceriodaphnia dubia, concentrations that cause reduced fecundity in the short (7-day) and long (5 generations) term should also cause changes in feeding rate and/or metabolism, measured as oxygen consumption. In addition, to test the hypothesis that an altered bioenergetic level caused by sodium sulfate exposure will affect the response of that organism to another toxicant, I measured the acute toxicity of phenol to C. dubia in the presence and absence of both food and sodium sulfate. Sodium sulfate reduced the filter-feeding rate of C. dubia, which was associated with significantly reduced oxygen consumption. This decreased energy level appeared to result in a consistent but decreased level of fecundity over a number of generations and the reproductive impairment was dose-dependent. These effects occurred at concentrations much lower than those at which acute (mortality) effects have been observed, a finding that may have regulatory implications. In addition, whereas phenol toxicity to C. dubia was exacerbated by the addition of food, increased phenol toxicity, likely induced by an increase in filtering or metabolic rate due to food addition, was negated when sodium sulfate was added to the test medium.     

Prenylated xanthones from <Emphasis Type="Italic">Hypericum ascyron</Emphasis>

Three new prenylated xanthones, 1,3,5-trihydroxy-6,7-[2′-(1-methylethenyl)-dihydrofurano]-xanthone (1), 1,3,5-trihydroxy-6,7-[2′-(1-hydroxy-1-methylethyl)-dihydrofurano]-xanthone (2), and 1,3,5-trihydroxy-6-O-prenyl-xanthone (3), together with eight known compounds were isolated from the leaves of Hypericum ascyron. Compound 3 has an O-prenyl moiety, and therefore represents the first reported xanthone to have an O-prenyl moiety from genus Hypericum. The structures of the isolated compounds were established based on spectroscopic data and on a comparison with values for previously identified analogues.     

Studies of the chemical composition of birch bark extracts (<Emphasis Type="Italic">Cortex betula</Emphasis>) from the <Emphasis Type="Italic">Betulaceae</Emphasis> family

This report presents the results obtained from chemical studies of the composition of dried birch bark extracts (DBBE) from Betula pubescens Ehrh. analyzed by GLC, HPLC, and IR and PMR spectroscopy. The extract contained the following groups of natural compounds: terpenoids (75.2%) and their esters (fatty acid esters of betulinol and lupeol, 4.4%), ether oils (0.08%), hydrocarbons (6.3%) and their epoxides (1.0%), steroids (β-sitosterol, 2.7%), tannins (2.1%), flavonoids (1.56%-mainly kaempferol, its 7-methyl ester, quercetin, the 4-methyl ester of naringenin, etc.), hydroxycoumarins (0.85%-umbelliferone, esculetin, etc.), and a number of unidentified compounds (about 4.0%). The major components of DBBE were triterpenoids and hydrocarbons. Preparative chromatographic separation of fractions containing triterpenoids and hydrocarbons yielded isolated samples which allowed the following compounds to be identified: the terpenoids betulinol, isobetulinol, lupeol, lupenone, betulonic aldehyde, betulonic acid, betulinic acid, and platanic acid, and the hydrocarbons α-santalene, β-trans-bergamotene, and α-trans-bergamotene, and their epoxy derivatives. The chemical composition of DBBE varied depending on the preparation method used, this particularly affecting the content of the major component betulinol, which varied from 54 to 82%. These studies led to the development of a contemporary preparative technology for betulinol with a yield of 95%, along with production of many of its acyl derivatives (for example, the diacetate, succinate, benzoate, etc.) with quite high yields (95–98%); betulinic acid was synthesized in mild conditions with a yield of at least 99.0%. These compounds are currently subject to pharmacological studies. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 8, pp. 22–26, August, 2007.     

Tropane alkaloids from <Emphasis Type="Italic">Erythroxylum emarginatum</Emphasis>

A tropane alkaloid, anhydroecgonine methyl ester N-oxide (2), was isolated for the first time as a naturally occurring compound, with anhydroecgonine methyl ester (1) from the bark of Erythroxylum emarginatum. Compound 1 was also isolated from the twigs. Their structures were elucidated mainly by spectroscopic methods.     

Constituents of the lichen <Emphasis Type="Italic">Peltigera dolichorrhiza</Emphasis>

A new aromatic derivative, 5-(3,4-dihydroxyphenyl)-3-methylcyclohex-2-enone (1), and three known compounds, peltigerine, solorinine, and phenyl butanoid, were isolated from the MeOH extract of the lichen Peltigera dolichorrhiza (Peltigeraceae). Their structures were determined by 1D and 2D nuclear magnetic resonance and mass spectroscopy analysis.