Glucose-conjugation of the flavones of Psiadia arabica by Cunninghamella elegans.

Microbial transformation of psiadiarabin and its 6-desmethoxy analogue 5,3' dihydroxy-7,2',4'5'-tetramethoxyflavone by Cunninghamella elegans NRRL 1392 gave the 3'-glucoside conjugates of the two flavones. Structural elucidation of these two new metabolites was achieved using 1D and 2D NMR spectroscopy and CIMS.

Labdane diterpenes from Otostegia fruticosa.

The new labdane diterpenes otostegin A (2), otostegin B (6) and 15-epi-otostegin B (7) were isolated from the aerial parts of Otostegia. fruticosa, besides the previously known labdanes preleoheterin (1), leoheterin (3), leopersin C and 15-epi-leopersin C (4, 5), ballonigrin (9) and vulgarol (11), along with the iridoid glucoside 8-O-acetylharpagide (10). The structure elucidation of all the isolated compounds was based on their spectral data and chemical derivatization.

A weakly antimalarial biflavanone from Rhus retinorrhoea.

The biflavanone (2S,2"S)-7,7"-di-O-methyltetrahydroamentoflavone and five known flavonoids, 7-O-methylnaringenin, 7,3'-O-dimethylquercetin, 7-O-methylapigenin, 7-O-methylluteolin, and eriodictyol were isolated from the leaves of Rhus retinorrhoea Steud, Ex Olive. The biflavanone exhibited moderate antimalarial activity with IC50 0.98 microg/ml against Plasmodium falciparum (W2 Clone) and weak activity against P. falciparum (D6 Clone) with IC50 2.8 microg/ml. Nevertheless, it did not display any cytotoxicity. 7-O-Methylnaringenin showed weak antimicrobial activity against Candida albicans, C. krusei, Staphylococcus aureus, Mycobacterium smegmatis, M. intracellulare, and M. xenopi with MIC approximately 100 microg/ml. Characterization of each compound was based on spectral analysis and comparison with reported data.

Alkaloids from Haplophyllum tuberculatum.

Two new alkaloids, haplotubinone (3) and haplotubine (4), were isolated from the aerial parts of Haplophyllum tuberculatum together with the known lignan diphyllin. The structures of the new alkaloids were established by spectroscopic methods in conjunction with X-ray crystallographic analysis of 3. In addition, the amide N-(2-phenylethyl)-benzamide has been identified in this source for the first time.

Microbial metabolism of artemisitene.

Studies on the microbial transformation of the sesquiterpene endoperoxide artemisitene have revealed that artemisitene was metabolized by Aspergillus niger (NRRL 599) to yield 11-epi-artemisinin, 9 beta-hydroxydeoxy-11-epi-artemisinin and 9 beta-hydroxy-11-epi-artemisinnin. These metabolites were characterized on the basis of their spectral data.

An evaluation of the male reproductive toxicity of cathinone.

(-)-Cathinone is the major psychoactive component of khat plant (Catha edulis Forssk.). Khat has been shown to produce reproductive toxicity in human beings and experimental animals. However, the chemical constituents of khat leaves responsible for sexual dysfunction are not known. In the present study cathinone enantiomers have been investigated for their reproductive toxicity in rats. Cathinone produced a dose-dependent decrease in food consumption and suppressed the gain in body weight. There was a significant decrease in sperm count and motility and increase in the number of abnormal sperms in cathinone treated animals. Histopathological examination of testes revealed degeneration of interstitial tissue, cellular infiltration and atrophy of Sertoli and Leydig's cells in cathinone treated animals. Cathinone also produced a significant decrease in plasma testosterone levels of the rats. Although both enantiomers of cathinone produced deleterious effects on male reproductive system, (-)-cathinone was found to be more toxic. From this study it may be concluded that the cathinone content in khat may be partially or totally responsible for the reproductive toxicity in khat chewers.

Comparative study of cathinone and amphetamine on brown adipose thermogenesis.

The effect of cathinone and amphetamine on brown adipose tissue thermogenesis and its modification with propranolol and timolol has been studied in rats. Both cathinone and amphetamine produced significant dose dependent increases in intracapsular brown adipose tissue (IBAT) and rectal temperatures. Amphetamine was found to be three times more potent as compared to cathinone, on a dose basis. Pretreatment of animals with propranolol and timolol individually inhibited cathinone and amphetamine induced hyperthermia. These findings suggest the involvement of beta adrenergic receptors in cathinone and amphetamine induced thermogenesis.

Isolation and characterization of the sesquiterpene lactones costunolide, parthenolide, costunolide diepoxide, santamarine, and reynosin from Magnolia grandiflora L.

The germacranolide sesquiterpene lactones costunolide, parthenolide, and costunolide diepoxide were isolated from the leaves of Magnolia grandiflora L. Costunolide diepoxide might be, at least in part, an artifact derived from air oxidation of parthenolide. The root bark yielded only costunolide together with the two eudesmanolides, santamarine and reynosin. In an attempt to synthesize costunolide diepoxide, the action of m-chloroperbenzoic acid on parthenolide and on costunolide was studied. The products were costunolide diepoxide from parthenolide and the two cyclized derivatives, santamarine and reynosin, from costunolide. The elusive 1,10-epoxide was obtained by epoxidizing costunolide using a biphasic system containing sodium bicarbonate. Under these conditions, epoxidation of costunolide took place without cyclization.

Antimicrobial activity of phenolic constituents of Magnolia grandiflora L.

Three phenolic constituents of Magnolia grandiflora L. were shown to possess significant antimicrobial activity using an agar well diffusion assay. Magnolol, honokiol, and 3.5'-diallyl-2'-hydroxy-4-methoxybiphenyl exhibited significant activity against Gram-positive and acid-fast bacteria and fungi. The minimum inhibitory concentrations were determined for each compound using a twofold serial dilution assay.

Clastogenic evaluation of cathinone and amphetamine in somatic cells of mice.

Clastogenic effects of cathinone, the active principle from khat (Catha edulis) and amphetamine, a compound having similar chemical structure and pharmacological activity, have been studied on the somatic cells of mice. Both of them produced marked clastogenic activity and affected the cell proliferation in the bone marrow of mice. They induced a significant increase in the frequency of micronucleated polychromatic erythrocytes at higher doses. These results substantiate our earlier observations on the clastogenic and mitodepressive activity of cathinone on the meristematic region of Allium cepa, and indicate that cathinone may be responsible for the mutagenic effect of khat reported by other workers. The clastogenic effects of amphetamine are being reported for the first time. Further studies are required to substantiate these findings and to study whether cathinone and amphetamine produce a direct clastogenic effect or whether they act as spindle poisons.

Antimicrobial activity of artemisinin and its derivatives against anaerobic bacteria.

Artemisinin and nine of its semisynthetic derivatives were tested for antibacterial activity against anaerobic, facultative anaerobic, microaerophilic and aerobic bacteria. Only anaerobic bacteria and gonococci showed sensitivity to artemisinin derivatives. Artemisinin and its deoxy derivatives had no activity at 100 micrograms/ml concentration. The newly synthesized methyl diperoxy derivative had the highest activity against all tested anaerobes with a MIC of 9.4 micrograms/ml.

Microbial hydroxylation and reduction of the diterpene psiadin.

Microbial bioconversion studies conducted on the diterpene psiadin have revealed that it was metabolized by Aspergillus niger (NRRL 2295) to give 2alpha-hydroxydeoxopsiadin, Cunninghamella blakesleeana (ATCC 8688a) to give 11beta-hydroxypsiadin, and Cylindrocephalum aureum (ATCC 12720), Gongronella butleri (ATCC 22822), Kloeckera africana (ATCC 20111), and Kluyveromyces marxianus var. lactis (ATCC 2628) to yield 7alpha-hydroxypsiadin. Their structures have been established on the basis of spectral data. The structure and relative stereochemistry of 7alpha-hydroxypsiadin was confirmed by single-crystal X-ray analysis.

Effect of khatamines and their enantiomers on plasma triiodothyronine and thyroxine levels in normal Wistar rats.

The effect of cathinone and N-formylnorephedrine, two psychoactive amines of khat (Catha edulis Forsk.) and their enantiomers have been studied on plasma levels of triiodothyronine (T3) and thyroxine (T4) in male Wistar rats. The rats were injected with 5, 10 and 30 mg/kg, body weight of four khatamines and the blood samples were collected 2 h after their administration. In the separate set of experiments the effect of these khatamines at 1, 2 and 4 h after their administration was also examined. All the khatamines failed to produce a significant dose dependent increase in T3 and T4 levels in the dose of 5 mg/kg. However, all of these compounds produced a significant dose dependent increase in T3 and T4 levels at higher doses but only T4 levels were increased following the dose of 10 mg/kg. Our studies on the effect of khatamines in T3 and T4 levels at various times showed a significant increase in T4 levels in all the four groups treated with various khatamines and the peak effect was observed at 2 h in case of (-)- and (+)-cathinone and 4 h in case of (-) and (+)N-formylnorephedrine. This study suggests that the symptoms observed in khat chewers including hyperthermia, anorexia, and metabolic changes may to some extent be attributed to the thyroid stimulating effect of khatamines. However, further studies are needed to establish the mechanism of release of thyroid hormones by these compounds and their involvement in the pharmacological effects.

Isolation and identification of an anti-inflammatory principle from Capparis spinosa.

The homologous polyprenols cappaprenol-12 (1), cappaprenol-13 (2) and cappaprenol-14 (3) with 12, 13 and 14 isoprene units, respectively, could be isolated by preparative HPLC from alcoholic extracts of Capparis spinosa. Testing 2 for its anti-inflammatory activity an inhibition of the carrageenan-induced paw edema in rats of 44 vs. 67% for the standard oxyphenbutazone was found.

Voltammetric determination of parthenolide in spiked human plasma and urine.

The voltammetric behaviour of parthenolide, a biologically active sesquiterpene lactone, was studied using direct current (DCt), alternating current and differential-pulse polarography (DPP). Parthenolide developed well-defined cathodic waves over the whole pH range in Britton-Robinson buffers. At pH 10 the diffusion current constant was 3.54 +/- 0.08 (+/- standard deviation; n = 8). The current vs concentration plots were rectilinear over the range 4-36 and 1-28 micrograms/mL in the DCt and DPP modes, respectively, with a minimum detectability of 0.06 microgram/mL (about 1 x 10(-7) M) using the latter technique. The waves were characterised as being diffusion controlled, although adsorption phenomenon played a limited role in the electrode process. The described analytical method was applied to the determination of parthenolide in spiked human urine and plasma; the percentage recoveries were 95.72 +/- 0.22 and 94.0 +/- 0.13 (+/- standard deviation; n = 9), respectively.

Separation and quantification of the major daucane esters of Ferula hermonis by HPLC.

A simple HPLC method was developed to quantify the major daucane sesquiterpene esters present in herb and roots of Ferula hermonis Boiss. The method utilized a C(18) reversed phase analytical column with isocratic elution for 30 minutes and UV detection at 240 nm. Extracts from two crude plant samples and two commercial products were fingerprinted and quantitatively analyzed.