SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
One fungus, Abisidia coerulea IFO 4011, and suspended cell cultures of one plant, Asparagus officinalis, were employed to bioconvert alpha- and 6beta-santonin. Incubation of alpha-santonin with the cell cultures of the fungus afforded two products, 11beta-hydroxy-alpha-santonin (1, in 76.5% yield) and 8alpha-hydroxy-alpha-santonin (2, in 2.0% yield). And from 6beta-santonin, four major products (3, 4, 5 and 6) and four minor products (7, 8, 9 and 10) were obtained, including 8alpha-hydroxylated products in trace yields. Very interestingly, a skeletal rearrangement occurred and a guaiane product (13) formed in a very low yield when alpha-santonin incubating with A.officinalis cell cultures, while not in the case of 6beta-santonin as substrate. Among the obtained 15 products, 2, 7, 8, 9, 10 and 12 are new compounds. The fact of 8alpha hydroxylation of santonin enables the formation of 8,12-eudesmanolide instead of 6,12-eudesmanolide and some useful modification at C-8 position. In addition, these reactions would provide evidence for the biogenesis between different types of eudesmane and/or guaiane compounds in the plants in nature.
Many sesquiterpene lactone compounds either induce or enhance the cell differentiation of human leukemia cells. However, we reported in a previous study that santonin, a eudesmanolide sesquiterpene lactone, exerts no effects on the differentiation of leukemia cells. In this report, to evaluate the possibility of chemically modifying santonin into its derivatives with differentiation inducing activity, we synthesized a series of santonin derivatives, and determined their effects on cellular differentiation in the human promyelocytic leukemia HL-60 cell system. A diacetoxy acetal derivative of santonin (DAAS) was found to induce significant HL-60 cell differentiation in a dose-dependent manner, whereas santonin in its original form did not. The HL-60 cells were differentiated into a granulocytic lineage when exposed to DAAS. In addition, the observed induction in cell differentiation closely correlated with the levels of NF-kappaB DNA binding activity inhibited by DAAS. Both Western blot analyses and kinase inhibitor studies determined that protein kinase C, ERK, and phosphatidylinositol 3-kinase were upstream components of the DAAS-mediated inhibition of NF-kappaB binding activity in HL-60 leukemia cells. The results of this study indicate that santonin can, indeed, be chemically modified into a derivative with differentiation inducing abilities, and suggest that DAAS might prove useful in the treatment of neoplastic diseases.
An investigation was undertaken to evaluate the comparative efficacy of single dose treatment with santonin and piperazine against naturally acquired Neoascaris vitulorum in sixty-two buffalo calves of 20-60 days of age. Santonin was administered orally in doses of 5 mg, 10 mg and 15 mg/kg body weight to thirteen, eighteen, and sixteen buffalo calves, respectively. As a control, piperazine (88 mg/kg) was given by drench to a group of fifteen infected buffalo calves. Pretreatment and post treatment faecal eggs per gram (EPG) counts were determined by the Stoll's technique. The percentage reductions in EPG counts on the third and seventh days after administration of the two drugs were calculated. The percentage reduction in EPG counts in the piperazine treated group on the third day was 82 +/- 15, 90.2 +/- 3 and 91.3 +/- 2.3% while on the seventh day these values were 88 +/- 16, 97 +/- 3, and 98 +/- 2% in high, moderate and heavy infection calves, respectively. Treatment with santonin at 5, 10 and 15 mg/kg body weight also reduced the EPG counts. The percentage reduction in EPG counts in the calves treated with 15 mg/kg of santonin on the third day was 92.3 +/- 18, 95.8 +/- 7 and 93.5 +/- 4% while on the seventh day these values were 100 +/- 0, 100 +/- 0 and 99.7 +/- 2% in high, moderate and heavily infected calves, respectively. Both piperazine and santonin were associated with some side effects like diarrhoea, restlessness, etc. but their percentage incidence was not significantly different from each other. These findings suggest that santonin in a 15 mg/kg dose has an efficacy similar to piperazine given at the 88 mg/kg dose level for the treatment of ascariasis in buffalo calves.
The microbial transformation of a sesquiterpene lactone, 1-alpha-santonin was carried out by Streptomyces roseochromogenes NRRL-B-1233. The product obtained from 1-alpha-santonin was purified using silica gel column chromatography with 1% acetone-benzene as the eluant. The molecular weight of the product was 248, estimated by mass spectroanalysis. The product was assigned the chemical structure of 1,2-dihydro-1-alpha santonin on the bases of 1H and 13C-NMR and mass spectroanalyses. Similar products were also obtained from other actinomycetes. The conversion of 1-alpha-santonin to 1,2-dihydro-1-alpha-santonin was 28% for Streptomyces roseochromogenes NRRL-B-1233, 14% for S. roseochromogenes ATCC 13400, 30.9% for S. aureofaciens KCC-S-0008, and 43.0% for S. aureofaciens KCC-S-0624, respectively.
Berberine and santonin were isolated from rhizomes of Berberis aristata and unexpanded flower buds of Artemisia maritima, respectively. Efficacy of these two chemicals individually as well as of their mixtures, was tested against spore germination of some saprophytic and obligate fungi. While berberine individually was effective against most of the fungi, Helminthosporium spp. were least affected even at the highest dose (1500 ppm). Santonin was equally effective against several fungi. Mixture of both alkaloids found to be more effective than individual ones. Keeping the dose of berberine constant and santonin at two different concentrations (viz. 250 and 500 ppm) the spore germination of Helminthosporium oryzae was stimulated. Increasing concentration of santonin inhibited the spore germination of all other fungi tested, Colletotrichum capsici being affected only by 20 and 5% (at berberine concentration of 250 and 500 ppm, respectively). On the other hand, santonin being constant and berberine at different concentrations, the mixture was effective against all the fungi.
The antipyretic activity of two sesquiterpene lactones, beta-santonin and arsubin, isolated from the lipid fraction of Artemisia coerulescens subsp. gallica was determined in rats along with the activity of alpha-santonin. In its alpha- and beta-forms, santonin caused a decrease in the body temperature of rats made febrile by the subcutaneous injection of beer yeast. This decrease, more pronounced in the case of beta-santonin, was dose-dependent and antagonized by pretreatment with haloperidol, an agent that also opposes the antipyretic activity of dopamine. These findings seem to show that the alpha- and beta-forms of santonin act on rectal temperature in a way similar to dopamine.
Fungal biotransformations of alpha-santonin (1) were conducted with Mucor plumbeus (ATCC 4740), Cunninghamella bainieri (ATCC 9244), Cunninghamella echinulata (ATCC 9245), Curvularia lunata (ATCC 12017) and Rhizopus stolonifer (ATCC 10404). Rhizopus stolonifer (ATCC 10404) metabolized compound 1 to afford 3,4-epoxy-alpha-santonin (2) and 4,5-dihydro-alpha-santonin (3) while Cunninghamella bainieri (ATCC 9244), Cunninghamella echinulata (ATCC 9245) and Mucor plumbeus (ATCC 4740) were capable of metabolizing compound 1 to give a reported metabolite, 1,2-dihydro-alpha-santonin (4). The structures of these transformed metabolites were established with the aid of extensive spectroscopic studies. These fungi regiospecifically reduced the carbon-carbon double bond in ring A of alpha-santonin.
Lady's finger plants (Hibiscus esculentus), grown in pots, were inoculated with the second-stage larvae (76+/-6) of root-knot nematodes Meloidogyne incognita, starting 7 days later they were treated with Cina 30c, Santonin 30c or Ethanol 30c by foliar spray for 10 consecutive days. The drugs in 90% ethanol were diluted with distilled water 1:1000 before application on plants. Thirty days after the last treatment the plants were uprooted. Cina 30c and Santonin 30c reduced nematode infestation of plants significantly in terms of root-gall number, root-protein content and nematode population in roots. Santonin 30c reduced root water content. Santonin 30c may have influenced the water channel proteins of root tissues thereby altering the water contents of roots. The reduced water content in roots might have adversely affected the root-knot nematodes and thus reduced nematode infestation. Ethanol 30c also has some effect on treated plants.
Santonin, a sesquiterpene lactone, commonly found in the plants of the family Compositae was found to show significant antiinflammatory activity on acute inflammatory processes. The activity profile of santonin closely resembled that of a standard non-steroidal antiinflammatory drug, diclofenac sodium. It also showed a significant inhibitory effect on granuloma formation; however, this effect of santonin was less pronounced as compared to diclofenac sodium. Santonin caused a significant antipyretic effect in mice, which was found to be independent of the route of administration of the drug. It also increased the hot plate reaction time of treated mice, similar to morphine.
Santonin gives a characteristic alkaline vs acidic difference spectrum. This was used for its estimation in pharmaceuticals and in the crude drug. Santonin was first extracted and purified through a specific partition procedure; then the difference absorbance was measured either at the maximum, 285 nm, or the minimum, 242 nm. The percentage of santonin can be calculated either by reference to the difference absorbance of a reference santonin sample, treated similarly, or by making use of the determined absorptivity. Measurement at the maximum is advisable, especially when the crude drug is assayed, because natural contaminants may interfere with the difference absorbance at the minimum.
The synthesis of two new santonin derivatives namely 3-oxo-6 beta-H-11 beta-phenylselenoeudesm-1,4-dien-6,13-olide and 3-oxo-6 beta H-eudesm-1,4,11-trien-6,13-olide is reported along with the results of a series of santonins tested for activity against the growth of KB cells in vitro, a human epidermoid nasopharynx carcinoma. Select compounds were found to be active at concentrations lower than 5 X 10(-5) M. In particular, the compound 2 alpha-bromo-3 beta-hydroxy-6 beta H-eudesm-11-en-6,13-olide exhibits an extremely low ID50 value at 0.33 X 10(-6) M. Some relationships between chemical structure and cytotoxic activity are suggested, i.e. the alpha-methylene-gamma-lactone moiety appears to be necessary for cytotoxic activity toward KB cells growth in vitro by santonin derivatives.