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F S el-Feraly

Publications and source records attributed to F S el-Feraly.

At least 19 recordsLinked to original sources
PubMed2001

Inhibitory effects of maesanin and analogs on arachidonic acid metabolizing enzymes.

The substituted 1,4-benzoquinone, maesanin (1), is a potent 5-lipoxygenase (5-LO) inhibitor present in the fruit of Maesa lanceolata Forssk. Thirteen natural, synthetic, semisynthetic, and microbially transformed analogs of 1 were tested for their in vitro inhibition of 5-lipoxygenase (5-LO) and cyclooxygenase-1 (COX-1). Maesanin was the most active 5-LO inhibitor. All other analogs were inactive or less active than the natural products as 5-LO inhibitors. None of the tested compounds was strongly active in the COX-1 inhibition assay.

Animals↗
PubMed2000

2-Hydroxy-5-(ethanolamino)-3-(10'-Z-pentadecenyl)-1,4-benzoquinone, new microbial phase II metabolite of maesanin.

The use of microbial models for biotransformation of the natural benzoquinone, maesanin (1), resulted in the isolation of an ethanolamine conjugate (5) from the culture broth of Debaryomyces polymorphus ATCC 20280. Metabolite 5 was characterized as 2-hydroxy-5-(ethanolamino)-3-(10'-Z-pentadecenyl)-1,4-benzoq uinone. The production of 5 represents a new type of phase II conjugation reaction in microbial systems. The results of preliminary mammalian metabolism of 1 in rats were inconclusive.

Acetylation↗
PubMed1999

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.

Artemisinins↗
PubMed1998

Artemisinin-derived sesquiterpene lactones as potential antitumour compounds: cytotoxic action against bone marrow and tumour cells.

We determined the in vitro cytotoxic activity of the sesquiterpene lactone endoperoxide artemisinin (1) and some chemically prepared derivatives, which have been found to display cytotoxicity to cloned murine Ehrlich ascites tumour (EAT) cells and human HeLa cells and against murine bone marrow using a clonogenic assay for committed progenitor cells of the granulocyte-monocyte lineage (CFU-GM assay). Comparing artemisinin (1) to deoxyartemisinin (2), the endoperoxide group appeared to play a role in cytotoxicity to CFU-GM cells. Dimers of dihydroartemisinin and dihydrodeoxyartemisinin revealed that the stereochemistry of the ether linkage of the dimers was a more important determinant for this cytotoxic activity. The nonsymmetrical dimer of dihydroartemisinin (3) and the corresponding endoperoxide-lacking dimer of dihydrodeoxyartemisinin (5) were equally cytotoxic to CFU-GM cells. Despite the differences between both systems, it may be stated that most compounds displayed higher cytotoxicity to CFU-GM cells than to EAT cells. Dimers of dihydroartemisinin (3, 4) were selected as potential antitumour compounds and subjected to the National Cancer Institute drug-screening programme consisting of about sixty human cancer cell lines derived from nine different tissues. Both compounds displayed the same specific cytotoxicity pattern. Throughout the screen dimer 3 was more active than 4.

Animals↗
PubMed1997

Stereochemistry-dependent cytotoxicity of some artemisinin derivatives.

We determined the cytotoxicity of some artemisinin derivatives against EN2 tumor cells using the MTT assay. Artemisinin (1) was clearly more cytotoxic than deoxyartemisinin (2), which lacks the endoperoxide bridge. Ether-linked dimers of dihydroartemisinin with defined stereochemistry were found to differ in the extent of cytotoxic effect on EN2 cells. The nonsymmetrical dimer (3) was more cytotoxic than the symmetrical dimer (4). The nonsymmetrical dimer of dihydrodeoxyartemisinin (5) lacking the endoperoxide bridges was also effective in the MTT assay, although less cytotoxic than 3 and 4. Similarly, the symmetrical dimer (6) was less effective than 5. Epoxides of artemisitene also showed that stereochemistry was an important factor for cytotoxicity. The results suggested that the endoperoxide bridge was not crucial for cytotoxicity to the tumor cells, but contributed to the cytotoxic effect apparently exerted by the ether linkage of the dimers. Flow cytometry data indicated that the dimers 3 and 4 caused an accumulation of the cells in the G1-phase of the cell cycle. In contrast, artemisinin (1) caused a slight increase of S-phase cells.

Antineoplastic Agents, Phytogenic↗
PubMed1997

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.

Biotransformation↗
PubMed1994

Microbial and mammalian metabolism studies of the semisynthetic antimalarial, anhydrodihydroartemisinin.

Microbial metabolism studies of the semisynthetic antimalarial anhydrodihydroartemisinin (1), have shown that it is metabolized by a number of microorganisms. Large scale fermentation with Streptomyces lavendulae L-105 and Rhizopogon species (ATCC 36060) have resulted in the isolation of four microbial metabolites. These metabolites have been identified as a 14-carbon rearranged product (2), 9 beta-hydroxyanhydrodihydroartemisinin (3), 11-epi-deoxydihydroartemisinin (4), and 3 alpha-hydroxydeoxyanhydrodihydroartemisinin (5). Microbial metabolites were completely characterized by spectral methods, including 1H-NMR and 13C-NMR spectroscopy. The structure and stereochemistry of metabolite 2 were unequivocally established by X-ray crystallographic analysis. Thermospray mass spectroscopy/high-performance liquid chromatographic analyses of plasma from rats used in mammalian metabolism studies of 1 have shown microbial metabolite 3 to be the major mammalian metabolite. In vitro antimalarial testing has shown metabolite 3 to possess antimalarial activity.

Animals↗
PubMed1993

Cytotoxicity of artemisinin-related endoperoxides to Ehrlich ascites tumor cells.

A series of artemisinin-related endoperoxides was tested for cytotoxicity to Ehrlich ascites tumor (EAT) cells using the microculture tetrazolium (MTT) assay. Artemisinin [1] had an IC50 value of 29.8 microM. Derivatives of dihydroartemisinin [2], being developed as antimalarial drugs (artemether [3], arteether [4], sodium artesunate [5], artelinic acid [6], and sodium artelinate [7]), exhibited a somewhat more potent cytotoxicity. Their IC50 values ranged from 12.2 to 19.9 microM. The presence of an exocyclic methylene fused to the lactone ring, as for artemisitene [9], led to higher cytotoxicity than 1. From the two epimeric 11-hydroxyartemisinin derivatives, the R form 12 showed a considerably higher cytotoxicity than the S form 13. Opening of the lactone ring of 1 dramatically reduced the cytotoxicity. The ether dimer 8 of 2 was the most potent cytotoxic agent, its IC50 being 1.4 microM. The variations in cytotoxicity between the structurally related compounds mostly correlated well with the theoretical capacity of radical formation and stabilization. In some cases lipophilicity or the presence of an electrophilic moiety seemed to have a determinant influence on cytotoxicity. The artemisinin-related endoperoxides showed cytotoxicity to EAT cells at higher concentrations than those needed for in vitro antimalarial activity, as reported in the literature.

Animals↗
PubMed1990

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.

Alkaloids↗
PubMed1990

Effects of artemisinin, dihydroartemisinin and arteether on immune responses of normal mice.

Artemisinin (Qinghaosu) is a potent antimalarial sesquiterpene lactone isolated from the Chinese herb Artemisia annua. Arteether, a potent semisynthetic analogue of dihydroartemisinin is being developed by the World Health Organization as the artemisinin derivative of choice for the treatment of malaria. All three agents in doses of 400 and 600 mg/kg body weight were found to exhibit marked suppression of humoral responses, as measured by the hemolytic plaque assay, with arteether being the most potent. These agents did not alter the delayed-type hypersensitivity response to sheep erythrocytes at the same dose levels. In addition, all three agents were found not to possess any anti-inflammatory activity when tested on carrageenan-induced oedema. These results indicated that these agents have a selective immunosuppressive activity. They did not exhibit immunostimulating activity in contrast to what has been reported for sodium artesunate.

Animals↗
PubMed1990

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.

Artemisinins↗
PubMed1990

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.

Alkaloids↗
PubMed1989

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.

Adipose Tissue, Brown↗
PubMed1988

Genetic effects of chronic treatment with cathinone in mice.

The mutagenicity of (-)-cathinone has been evaluated in the germ cells of male albino mice using a dominant lethal test. An aqueous solution of cathinone was administered orally at doses of 5, 20 or 40 mg/kg body wt, respectively to three different groups of male mice for a period of six weeks. After treatment, each male was allowed to mate with two different groups of three females each, on two consecutive weeks. These females were necropsied on the 17th day after mating. The number of implants in each female and the ratio of live and dead embryos was determined. The results of this study showed that treatment of male mice over a period of 6 weeks produced a dose-dependent reduction in fertility with total sterility at a dose of 40 mg/kg body wt. Cathinone also induced dose-dependent post-implantation loss during the first week following treatment. However, no dominant lethality was detected during the second week of mating.

Alkaloids↗
PubMed1988

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.

Animals↗
PubMed1987

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.

Alkaloids↗
PubMed1978

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.

Cyclization↗