Synthesis and antiviral activity of novel<Emphasis Type="Italic">trans</Emphasis>-2,2-dimethyl cyclopropyl nucleosides

Novel trans-2,2-dimethylcyclopropyl nucleosides were synthesized as potential antiviral agents. The key intermediate, 3, was synthesized via five steps from ethyl chrysanthemate and condensed with purine bases using the Mitsunobu reaction to give six cyclopropyl nucleosides. These synthesized nucleosides did not show any significant antiviral activity against HSV-1, HSV-2, EMCV, Cox B3, or VSV, at concentrations up to 100 microM.     

Synthesis and antiviral activity of novel<Emphasis Type="Italic">c</Emphasis>-methyl branched cyclopropyl nucleosides

A series of novel cyclopropyl nucleosides was synthesized using the highly stereoselective Simmons-Smith reaction starting from 1,2:5,6-di-O-isopropylidene-D-mannitol. The structural assignments of these nucleosides were determined by NMR studies and X-ray crystallography. All the synthesized nucleosides were assayed against several viruses.     

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.     

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.     

Synthesis and analgesic activity of 4-aroyl-1<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">c</Emphasis>]oxepin-3-ones

A series of 4-aroyl-1H-benzo[c]oxepin-4-ones have been prepared by heating ethyl 2-aroyl-3-(2-bromophenyl)propenoates. The synthesized compounds possess higher analgesic activity than the reference drug (analgin) and exhibit low toxicity.     

(<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.     

Synthesis and biological activity of substituted 6-alkyl(6<Emphasis Type="Italic">H</Emphasis>)-3-phenyl-1,2,4-triazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]-1,3,4-thiadiazines

A series of substituted 6-alkyl(6H)-3-phenyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines have been synthesized by reaction of 3-alkyl-4-amino-5-thio-1,2,4-triazoles with substituted phenacylbromides in the presence of an equimolar amount of KOH. Mass spectra for the dissociative ionization by electron impact, antibacterial activity, and antitumor properties of the synthesized compounds have been studied. It was established that some compounds at doses of 50 – 100 mg/kg decrease the growth of sarcomas 45 and 37 by 35 – 47%.     

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.     

Synthesis and anti-inflammatory activity of 3,1-benzoxazin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones and <Emphasis Type="Italic">N</Emphasis>-acyl-5-iodoanthranilic acid amides

A series of new 3,1-benzoxazin-4(3H)-ones were synthesized and N-acyl-5-iodoanthranilic acid amides derived from them were obtained in a search for new biologically active derivatives of anthranilic acid. The anti-inflammatory activity of these compounds was evaluated. It is established that these classes of compounds are promising for further research on biologically active substances possessing anti-inflammatory activity. Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 42, No. 12, pp. 19–18, December, 2008.     

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.     

Use of nanoparticles to increase the systemic bioavailability of <Emphasis Type="Italic">trans</Emphasis>-resveratrol

Resveratrol is a substance of plant origin with antioxidant, anti-inflammatory, and chemoprotective properties used as a biologically active supplement in the prophylaxis of myocardial infarction, types 1 and 2 diabetes, and tumors. The aim of the present work was to develop and perform pharmacokinetic studies of a nanosomal form of resveratrol. The techniques described here yield particles of submicron size, with resveratrol yields of 70–100% and resveratrol contents in lyophilized formulations reaching 15–20%. After oral administration of unmodified resveratrol to mice, only 19% of the dose was taken up into the blood, while use of nanosomal resveratrol formulations based on Eudragit RL and lecithin/chitosan increased bioavailability to 39% and 61% respectively. Increases in the peak plasma resveratrol concentration by factors of 4–5 were also seen in mice given nanoparticles. Thus, conversion of resveratrol to the nanosomal form leads to solubilization and resultant increases in absorption into the bloodstream.     

New potential antihypoxants based on 2-ethyl-3-(<Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-dimethylcarbamoyloxy)-6-methylpyridine

It is established that succinic acid is capable of potentiating (synergism) the antihypoxic activity of 3-hydroxypyridine derivatives such as the succinate (Ia) and hydrochloride (Ib) of 3-(N,N-dimethylcarbamoyloxy)- 2-ethyl-6-methylpyridine. This effect makes it expedient to create new drugs containing a mixture of Ia or Ib and succinic acid derivatives that would possess antihypoxic, antiamnestic, and anticonvulsant activity. The antihypoxic activity of 3-hydroxypyridine drugs increases in the order emoxypin < mexidol < proxypin < Ia + succinic acid < Ib + succinic acid.     

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 neurotropic activity of substituted 5-dialkylaminoacetyl-3a,4,5,9b-tetraydro-3<Emphasis Type="Italic">H-</Emphasis>cyclopenta[<Emphasis Type="Italic">c</Emphasis>]quinolines

A series of substituted 5-dialkylaminoacetyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolines were synthesized by amination of the corresponding 5-chloroacetyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolines. The acute toxicity, analgesic activity, and influence of the obtained compounds on the locomotor and exploratory activity in the open-field test were studied.