6-Nitrobenzimidazole derivatives: potential phosphodiesterase inhibitors: synthesis and structure-activity relationship.

6-Nitrobenzimidazole derivatives (1-30) synthesized and their phosphodiesterase inhibitory activities determined. Out of thirty tested compounds, ten showed a varying degrees of phosphodiesterase inhibition with IC(50) values between 1.5±0.043 and 294.0±16.7 µM. Compounds 30 (IC(50)=1.5±0.043 µM), 1 (IC(50)=2.4±0.049 µM), 11 (IC(50)=5.7±0.113 µM), 13 (IC(50)=6.4±0.148 µM), 14 (IC(50)=10.5±0.51 µM), 9 (IC(50)=11.49±0.08 µM), 3 (IC(50)=63.1±1.48 µM), 10 (IC(50)=120.0±4.47 µM), and 6 (IC(50)=153.2±5.6 µM) showed excellent phosphodiesterase inhibitory activity, much superior to the standard EDTA (IC(50)=274±0.007 µM), and thus are potential molecules for the development of a new class of phosphodiesterase inhibitors. A structure-activity relationship is evaluated. All compounds are characterized by spectroscopic parameters.

An investigation of the kinetic and anti-angiogenic properties of plant glycoside inhibitors of thymidine phosphorylase.

We investigated the potential of symplocomoside (1) and symponoside (2), glycosides isolated from the bark of Symplocos racemosa to inhibit thymidine phosphorylase (TP) activity and associated angiogenesis. Compound 1 was a reversible, noncompetitive inhibitor of deoxythymidine binding to TP (IC(50) = 65.45 +/- 5.08 microM; K(i) = 62.83 +/- 2.10 microM) and 2 was a reversible, uncompetitive inhibitor (IC(50) = 94.17 +/- 4.05 microM; K(i) = 101.95 +/- 1.65 microM). Molecular modeling analysis indicated that both compounds bound at the active site of the enzyme but not solely to amino acid residues involved in catalysis. Both compounds were active in in vitro angiogenic assays inhibiting endothelial cell migration and invasion in Matrigel, but did not inhibit growth factor-induced proliferation and were not cytotoxic. Compound 1 may have potential as an anti-angiogenic and anti-tumor agent.

Kinetics studies on the lignan class of natural compounds that inhibits alpha-chymotrypsin.

The mechanism of inhibition of the alpha-chymotrypsin enzyme by two lignans of the fused bistetrahydrofuran series, epiexcelsin (1) and 5'-demethoxyepiexcelsin (2), which were isolated from the Commiphora mukul Engl., was investigated. Lineweaver-Burk and Dixon plots and their secondary replots showed that these compounds were noncompetitive inhibitors of the enzyme. K(i) values for 1 and 2 were found to be 22.29 +/- 0.015 and 336.30 +/- 0.053 microM, respectively.

Two new lignan glycosides from Trachelospermum lucidum (D. Don) Schum.

Two new lignans (1 and 2) having a diarylhydroxybutyrolactone skeleton were isolated from the leaves of Trachelospermum lucidum (D. Don) Schum. Their structures were elucidated to be apocynotrachelolegnin 5'-O-beta-d-glucopyranoside (1) and rafanotrachelogenin 4-O-beta-d-glucopyranoside (2) on the basis of spectroscopic analysis. Two known lignans, matairesionoside-4-O-beta-d-glucoside (3) and trachelosiaside (4), were also isolated from Trachelospermum lucidum.

New salirepin derivatives from Symplocos racemosa.

The phytochemical investigation of the n-butanol soluble fraction of the bark of stem of Symplocos racemosa Roxb. yielded two new phenolic glycosides of salirepin series, symplocuronic acid (1) and sympocemoside (2), while salirepin (3) was isolated for the first time from this plant. The structures of the new compounds were identified by 1D and 2D NMR techniques along with other spectral evidences and by comparison with the published data of closely related compounds.

A new acylated flavone glycoside from the fruits of Stocksia brauhica.

Phytochemical investigations of the fruits of Stocksia brauhica (Sapindaceae) resulted in the isolation of a new acylated flavone glycoside. Its structure of the new compound brauhenefloroside D (1) was established as 3-O-[(alpha-L-rhamnopyranosyl)oxy]-7-O-[(acetyl)-beta-D-glucopyranosyl (1 --> 4)]-[6-O-(4-hydroxy-E-cinnamoyl)-beta-D-glucopyranosyl-(1 --> 2)-alpha-L-rhamnopyranosyl)-oxy]-kaempferol. The structure elucidation of the new compound was based primarily on 1D and 2D NMR analysis, including COSY, HMBC and HMQC correlations.

Two new trans-clerodane diterpenoids from Otostegia limbata.

Two new tricyclic clerodane-type diterpenoids, limbatolide D (1) and limbatolide E (2), have been isolated from the roots of Otostegia limbata. Their structures and the relative configuration were established on the basis of spectral methods, especially two-dimensional (2D) NMR techniques.

Antimicrobial activity of seed extracts and bondenolide from Caesalpinia bonduc (L.) Roxb.

The antibacterial and antifungal activities, along with a phytotoxicity test of the newly isolated diterpene bondenolide (1), of a methanol extract, ethylacetate fraction and water soluble part of the methanol extract of Caesalpinia bonduc (L.) Roxb. were assayed.

Isolation and structure analysis of a glucomannan from the seeds of Libyan dates.

Polysaccharides extracted from seeds of Libyan dates with hot ethanol 80% (FI) and 0.1 M phosphate solution (FII) were fractionated and purified by ion-exchange and gel-filtration chromatography. According to methylation and hydrolysis analysis, the main chains of FI and FII consisted of (1-->4)-linked glucomannan; only traces of branched sugar residues were detected. This is the first report on the isolation of glucomannan from date seeds.

Coumarins from the aerial part of Halocnemum strobilaceum.

Four known coumarins, coumarin (1), 7-hydroxy-3-methylcoumarin (2), oreoselone (3) and heraclenin (4), were isolated from aerial part of Halocnemum strobilaceum. Their structures were determined by 1 and 2-D NMR techniques.

Novel cycloartane saponins from Corchorus depressus L.

Two novel bidesmosidic cycloartane-type glycosides, depressosides C and D were isolated from Corchorus depressus L. Their structures were elucidated as (22R)-16beta,22-epoxy-3beta,26-dihydroxy-9,19-cyclolanost-++ +24E-ene 3, 26-di-O-beta-D-glucopyranoside and (22R,24S)-22,25-epoxy-3beta,16beta,24-trihydroxy-9,19-cyclolano stane 3, 24-di-O-beta-glucopyranoside, respectively on the basis of chemical evidence and detailed spectroscopic studies.

Taraxacin, a new guaianolide from Taraxacum wallichii.

A new guaianolide, taraxacin (1), and a known sesquiterpene ketolactone (2) have been isolated from an ethyl acetate-soluble part of a methanolic extract of Taraxacum wallichii. The structure of 1 was established using NMR, MS, and X-ray crystallographic methods. The (13)C NMR data of 2 is also being reported for the first time.

Chemical constituents from Asparagus dumosus.

The isolation and characterization of calonysterone (1), blechnoside B (2), 20-hydroxyecdysone and isovanillin from the whole plant of Asparagus dumosus are being reported for the first time from this source.

Chemistry of Zataria multiflora (Lamiaceae).

The hexane soluble part of Zataria multiflora afforded three new aromatic constituents which include two p-cymene derivatives: multiflotriol (1), multiflorol (2) and an aromatic ester of p-hydroxy benzoic acid (3). In addition to these three new compounds, three known compounds, dihydroxyaromadendrane, luteolin and alpha-tocopherolquinone, have also been isolated for the first time from the same source. The structures of all the isolated constituents were elucidated by means of spectroscopic methods including 2D-NMR techniques.

Caulerpin.

The crystal structure of caulerpin (dimethyl 6,13-dihydrodibenzo[b,i]phenazine-5,12-dicarboxylate, C(24)H(18)N(2)O(4)), an indole alkaloid, reported in space group Cc with an acute beta angle, has been redetermined in the correct space group, C2/c. The molecule has twofold crystallographic symmetry and is composed of two essentially planar indole groups fused to an eight-membered cyclooctatetraene ring which adopts a boat conformation. The molecular dimensions are normal. The structure is stabilized by intermolecular and intramolecular interactions involving the indole N-H atom and carbonyl O atom [N.O 3.211 (4) and 2.836 (4) A].

Phytochemical study of Salvia moorcroftiana.

Four known flavonoids were isolated from the aerial parts of Salvia moorcroftiana.

Pyrrolizidine alkaloids from Senecio lorenthii.

The isolation and NMR spectra of otosenine (1) and seneciphylline (2) from Senecio lorenthii are reported.

Cytotoxic activity of marine macro-algae on Artemia salina (brine shrimp).

A total of 22 ethanol extracts of seaweed species (13 brown, 6 green and 3 red) collected from the Karachi coast were investigated for brine shrimp cytotoxicity. Of all the species, only six namely Stoechospermum marginatum, Sargassum swartzii, S. binderi, Spatoglossum asperum, Stokeyia indica (brown) and Caulerpa racemosa (green) showed significant activity. n-Hexane-soluble fractions of the ethanol extract of S. marginatum and S. swartzii were found to be responsible for the activity, whereas the methanol-soluble fractions of S. asperum and S. binderi were most active. The water extract of S. indica and C. racemosa exhibited the most prominent activity (LC50 value below 70 micrograms/mL) when compared with the ethanol extracts and their fractions. Cytotoxic activity may be due to the compounds differing in polarity.

Steroidal saponins from Asparagus dumosus.

A new steroidal saponin, dumoside, characterized as (20S)-3 beta, 16 beta-dihydroxy pregn-5-ene-22-carboxylic acid (22, 16)-lactone-3-O-beta-chacotrioside, was isolated from the whole plant of Asparagus dumosus Baker and the structure was deduced from spectral data. In addition to dumoside three more steroidal saponins characterized as 3 beta-dihydroxy pregn-5,16-dien-20-one 3-O-beta-chacotrioside, 3 beta, 22 alpha, 26-trihydroxyfurost-5-ene-3-O-beta-chacotrioside-26-O- beta-D-glucopyranoside and its corresponding 22 alpha-O methoxy analogue were also isolated for the first time from this source. The structures have been identified with the help of FAB-MS, 1H NMR, 13C NMR and extensive 2D NMR spectroscopy, as well as comparison with reported spectroscopic data.

Bucharioside and buchariol from Salvia bucharica.

A new monoterpene-glycoside (2-exo-beta-D-glucopyranosyl-1,8-cineol) named bucharioside from the methanol-soluble part and a new sesquiterpenoid (4,10-epoxy-6alpha-hydroxyguaiane) named buchariol from the hexane-soluble part of Salvia bucharica were obtained. Their structures were elucidated with the help of NMR spectroscopy including 1D and 2D experiments.