Acetogenins from seeds of Annona reticulata

Chromatography of an ethyl acetate extract of seeds of Annona reticulata led to the isolation of a new cytotoxic gamma-lactone acetogenin, cis-/trans-isomurisolenin, along with six known cytotoxic acetogenins, annoreticuin, annoreticuin-9-one, bullatacin, squamocin, cis-/trans-bullatacinone and cis-/trans-murisolinone. Structures of these compounds were established by means of mass and related spectral experiments. Some of the compounds isolated, showed potent cytotoxicities against Hep. 2,2,15, Hep. G2, KB and CCM2, four cancer cell-lines.     

Studies on the acetogenins of Formosan annonaceous plants. II. Cytotoxic acetogenins from Annona reticulata

Using cytotoxicity as a guide to fractionation, one novel acetogenin, annoreticuin-9-one [3], and four known cytotoxic acetogenins, squamone [4], solamin [5], annomonicin [6] and rolliniastatin 2 [7], were isolated from active extracts of the leaves of the Formosan plant Annona reticulata. Their structures were elucidated on the basis of uv, ir, 1H- and 13C-nmr, and ms data of the natural compounds and their derivatives.     

Purpurediolin and purpurenin, two new cytotoxic adjacent bis-tetrahydrofuran annonaceous acetogenins from the seeds of Annona purpurea

PURPOSE: This study investigated the different effects of quantitative percentages of glass fiber intensity on the transverse strength, maximum deformation, and the modulus of elasticity of acrylic resin. MATERIALS AND METHODS: Fifty-four specimens were formed in a specially designed mold to produce identical specimens in accordance with the manufacturer's recommendations. Six percentages of glass fiber reinforcement in loose random form were studied. Each glass fiber treatment percentage (0%, 1%, 2%, 5%, 10%, 15%) was related to the total powder/liquid mass. RESULTS: The results indicated that 1% glass fiber treatment enhanced the transverse strength of the tested specimen. Maximum deformation at failure in the tested treatment groups was found to be different. The interaction of glass fiber concentration on fracture strength and deformation was significant (p < 0.0001). CONCLUSION: The 1% glass fiber concentration was found to give the best fracture strength and deformation results. Significantly higher glass fiber percentages was found to weaken the resin.     

Disposition and metabolism of some nitrofurylthiazoles possessing antiparasitic activity

1. The absorption, distribution and excretion of two 35S-labelled nitrofurylthiazole analogues have been investigated in rats and mice. The compounds are not well absorbed. Higher plasma and tissue levels are reached when more water-soluble analogues are administered. 2. Metabolic transformations of these two compounds and other membranes of the series include reduction of the nitro group, degradation of the furan ring and oxidation of the terminal alicyclic and aliphatic functions. 3. Metabolic cleavage of a morpholine ring to form an hydroxy-acid has been demonstrated for one member of the series.     

5-Methylflavasperone and rhamnetin from Guiera senegalensis and their antioxidative and 5-lipoxygenase inhibitory activity

From the methylene chloride extract of the leaves of Guiera senegalensis a novel naphthopyran, 5-methylflavasperone (5,8,10-trimethoxy-2-methyl-4 H-naphtho[1,2-b]pyran-4-one), as well as rhamnetin were isolated. Rhamnetin showed a strong inhibitory activity on 5-lipoxygenase from porcine leucocytes with an IC50 value of 0.7 microM whereas 5-methylflavasperone revealed only a weak inhibitory activity (IC50 > 200 microM). In the deoxyribose assay both compounds exerted similar antiradicalar effects (IC50 15.8 and 16.7 microM, respectively). In another assay only rhamnetin inhibited peroxidation of phospholipid liposomes (IC50 = 2.4 microM). For 5-methylflavasperone no dose dependent inhibition could be observed.     

Conformation and activity of mannose- and N-acetylgalactosamine-specific lectins from Vicia villosa seeds

The conformation of two Vicia villosa lectins specific for mannose and N-acetylgalactosamine, respectively, was studied by circular dichroism. Both showed a broad negative CD band around 220 nm and a positive one above 190 nm. CD data analysis indicated that they were rich in beta-sheet. However, they differed in conformational stability against extreme pH, at elevated temperature, and in guanidine hydrochloride and sodium dodecyl sulfate solutions. The unusual feature was that the conformation of N-acetylgalactosamine-specific lectin was virtually unaltered in 6 M guanidine hydrochloride and 7.5 mM surfactant.     

Cytotoxic activity of platelets and peripheral blood mononuclear cells from oncology patients and healthy donors

Testicular germ cell tumour is said to be a model for curable neoplasm. However, the prognosis of primary extragonadal germ cell tumour does not appear to be as promising. Though similar in histology, the biology of primary extragonadal germ cell tumour is different as exemplified by the patients in this review. Eight patients with primary mediastinal germ cell tumours were treated with intensive cisplatin-based chemotherapy. All, except one, had non-seminomatous components. The poor prognosis of mediastinal germ cell tumour is due to a combination of poor treatment results with the cisplatin-based regimen and the development of non-germ cell and haematological malignancies.     

Glabracins A and B, two new acetogenins from Annona glabra

Two new bioactive bis-THF Annonaceous acetogenins, glabracins A (1) and B (2), and two previously known acetogenins, javoricin (3) and bullatanocin (4), have been isolated from the leaves of Annona glabra by activity-directed fractionation using the brine shrimp lethality test (BST). The structures of 1 and 2 were elucidated based on spectroscopic and chemical methods, and the absolute stereochemistries were partially determined by the advanced Mosher ester method. 1 and 2 showed selective cytotoxicities to certain human tumor cell lines, and 1 was significantly more potent although 1 and 2 differ only in the stereochemistry of their vicinal diols at C-23/24.     

Cytotoxic isoflavans from Eysenhardtia polystachya

Two new cytotoxic isoflavans, (3S)-7-hydroxy-2',3',4',5', 8-pentamethoxyisoflavan (1) and (3S)-3',7-dihydroxy-2',4',5', 8-tetramethoxyisoflavan (2), were isolated from the bark and trunks of Eysenhardtia polystachya (Leguminosae), together with the known constituents stigmasterol, isoduartin, cuneatin, 7-hydroxy-2',4', 5'-trimethoxyisoflavone, and 3,4-dimethoxy-8, 9-(methylenedioxy)pterocarpan. The structures of 1 and 2 were elucidated on the basis of spectroscopic methods. The antimicrobial, cytotoxic, and insecticidal potential of some of these compounds were evaluated. The isoflavans 1, 2, and isoduartin (2', 7-dihydroxy-3',4',8-trimethoxyisoflavan) displayed moderate cytotoxic activity against KB cell lines.     

Cytotoxic lignans from Formosan Hernandia nymphaeifolia

The autolytic site Arg105 of rat trypsin was replaced with Cys by DNA site-directed mutagenesis method. Comparison of expression and purification of R105C trypsin along with the wild type and some other Arg105 mutants indicates that R105C trypsin could be expressed as well but with a lower expression level. It is unexpected that R105C trypsin has no detectable activity toward trypsin substrate TAME, quite different from the wild type and other Arg105 mutants. Native gel electrophoresis analysis indicates that R105C trypsin has a similar mobility rate to that of wild type trypsin. FPLC also gives similar retaining time. The loss of activity of R105C trypsin may result from the conformational change around active site, but not the dimer formation.     

Cytotoxic sesquiterpene lactones from Inula britannica

Cytotoxicity-guided fractionation of the flowers of Inula britannica led to the isolation of four sesquiterpene lactones, 4 alpha, 6 alpha-dihydroxyeudesman-8 beta, 12-olide (1), ergolide (2), 8-epi-helenalin (3), and bigelovin (4). Compound 1 was isolated as a new natural product. These compounds showed cytotoxicity against human tumor cell lines.     

Glacins A and B: two novel bioactive mono-tetrahydrofuran acetogenins from Annona glabra

OBJECTIVE: Using the DSM-IV diagnostic criteria for acute stress disorder, the authors examined whether the acute psychological effects of being a bystander to violence involving mass shootings in an office building predicted later posttraumatic stress symptoms. METHOD: The participants in this study were 36 employees working in an office building where a gunman shot 14 persons (eight fatally). The acute stress symptoms were assessed within 8 days of the event, and posttraumatic stress symptoms of 32 employees were assessed 7 to 10 months later. RESULTS: According to the Stanford Acute Stress Reaction Questionnaire, 12 (33%) of the employees met criteria for the diagnosis of acute stress disorder. Acute stress symptoms were found to be an excellent predictor of the subjects' posttraumatic stress symptoms 7-10 months after the traumatic event. CONCLUSIONS: These results suggest not only that being a bystander to violence is highly stressful in the short run, but that acute stress reactions to such an event further predict later posttraumatic stress symptoms.     

Cytotoxic and antitumour principles from Ixora coccinea flowers

Susceptibility of four major rat tissues to oxidative damage in terms of lipid peroxidation induced by in vitro by ascorbate-Fe2+ in homogenates and mitochondria has been examined. Lipid peroxidation, as assessed by thiobarbituric acid reactive substances (TBARS) and conjugated dienes was maximum in brain followed by liver, kidney and heart. However, the time course of lipid peroxidation showed different patterns in tissues examined. The higher susceptibilities of brain and liver can be explained by substrate availability and to a lesser extent the level of antioxidants. The differences observed in the tissues studied may reflect their susceptibility to degenerative diseases and xenobiotic toxicity which are considered as a result of oxidative damage to membranes.     

Cytotoxic and leishmanicidal aminoglycosteroids and aminosteroids from Holarrhena curtisii

The EtOH extract of the leaves of Holarrhena curtisii yielded five new steroidal alkaloids: 17-epi-holacurtine (3), 17-epi-N-demethylholacurtine (4), holacurtinol (5), 3alpha-amino-14beta-hydroxypregnan-20-one (7), and 15alpha-hydroxyholamine (8), in addition to the known compounds, holacurtine (1), N-demethylholacurtine (2), and holamine (6). All eight compounds showed significant cytotoxic and leishmanicidal activities.     

Annojahnin from Annona jahnii: a possible precursor of mono-tetrahydrofuran acetogenins

A new cytotoxic Annonaceous acetogenin, annojahnin (1), was isolated from the twigs of Annona jahnii (Annonaceae) by bioactivity-directed fractionation using lethality to brine shrimp. Compound 1 represents an unusual type of C-37 Annonaceous acetogenin, lacking either tetrahydrofuran (THF) or epoxide rings, bearing a keto group at C-10, and possessing a double bond located two methylenes away from a vicinal diol. The structure and absolute configuration of 1 were elucidated by 1H and 13C NMR, COSY, and single-relayed COSY and from chemical derivatives. 4-Deoxy-18/21-trans-annomontacin 10-one (4) and 4-deoxy-18/21-cis-annomontacin-10-one (5), two semisynthetic mono-THF acetogenins, were prepared from 1 by reactions that mimic the biogenetic pathways. These acetogenins showed selective cytotoxicities, comparable or superior to adriamycin, among six human solid tumor cell lines. Reduction of the 10-keto of 1, to the racemic 10-OH derivative (3), retained the bioactivities as did the conversion of 1 to 4 and 5.     

Synthesis and antiparasitic activities of amidinic azolated derivatives

The natural immunity status in different age groups was investigated. The positive rate of HI antibody under the age of 4 was less than 25%. The natural immunity level increased gradually with age and the positive rate of the antibody reached 80% among the group aged 13-25. Rate of seroconversion was 100% in any age group one month after immunization, and GMT rose from 13.33 to 243.16. It was suggested that immunogenicity of domestic attenuated live rubella vaccine BRD II was satisfactory. For the population with positive-antibody before immunization, the total GMT rose from 189.59 to 259.00 after vaccination and the difference between immunization before and after was highly significant. According to the above result, we suggested that the vaccination strategy for rubella among young children and women of child-bearing age should be implemented.     

Cytotoxic and ichthyotoxic compounds from marine Opisthobranchia and soft coral

Epidural analgesia in labour using local anaesthetics is very efficient, but the technique has been associated with undesired motor block and an increased use of instrumental deliveries. A new epidural analgesia technique, using a combination of low-dose local anaesthetics and opioids (fentanyl and sufentanil), has recently come into practice. The new epidural technique provides excellent analgesia, minimises motor block, allows the mother to ambulate, and minimises the need for instrumental delivery. Furthermore, it constitutes a good alternative to parenteral pethidine. We are of the opinion that all pregnant women should be given detailed information about both the benefits and the possible side-effects of epidural analgesia in good time before they go into labour. This will allow them to participate more actively in deciding whether or not to use analgesia during labour. Optimal use of epidural analgesia not only depends on the availability of a 24-hour anaesthesia service, but also on adequate knowledge and the cooperation and enthusiasm of all those involved, namely midwives, obstetricians and anaesthesiologists.     

Analysis of kafirin promoter activity in transgenic tobacco seeds

Sequences corresponding to 855 bp of 5' promoter region and the transit peptide from lambdaGK.1,a genomic clone encoding a 22 kDa alpha-kafirin seed protein from sorghum, were translationally fused to a cloned beta-glucuronidase (GUS) coding sequence from uidA and transferred to tobacco via Agrobacterium tumefaciens-mediated transformation. No GUS expression was detectable at any stage of growth in stems or leaves of these plants. However, GUS expression was detected in both embryo and endosperm tissues of resulting tobacco seeds 10-15 days after flowering. Dissected tissues indicate endosperm expression was localized within the bulk endosperm and not within the parenchyma cell layer underlying the integument. These studies also demonstrate that within dissected tobacco embryos, expression from the kafirin promoter was restricted to the mesocotyl region.     

Conformational preference for segetalins G and H, cyclic peptides with estrogen-like activity from seeds of Vaccaria segetalis

Three-dimensional structures in DMSO-d0 of segetalins G [cyclo(-Gly-Val-Lys-Tyr-Ala-)] and H [cyclo(-Gly-Tyr-Arg-Phe-Ser-)], cyclic pentapeptides from seeds of Vaccaria segetalis, showing estrogen-like activity, were determined by the distance geometry calculation and restrained energy minimization from NMR data. The backbone structure of segetalin G contains one beta-turn: a beta II-like turn at Tyr4-Ala5, and that of segetalin H one beta-turn: a beta II' turn at Gly1-Tyr2 and one gamma-turn at Arg3-Phe4-Ser5 sequence. The results of distance comparison analysis proposed a pharmacophore model of estrogen-like cyclic peptides, segetalins.     

Two new 7-dehydroaporphine alkaloids and antiplatelet action aporphines from the leaves of Annona purpurea

Bioactivity-directed fractionation led to the isolation of two new 7-dehydroaporphine alkaloids, 7-hydroxy-dehydrothalicsimidine (1) and 7-formyl-dehydrothalicsimidine (2), along with the five known alkaloids, thalicsimidine (3), norpurpureine (4), N-methyllaurotetanine (5), lirinidine (6) and N-methylasimilobine (7), from the leaves of Annona purpurea. Structural elucidation of these compounds was established by mass and spectroscopic analyses. Among them, 1, 3, 4, 6 and 7 exhibited significant inhibition of collagen, arachidonic acid and platelet activating factor-induced platelet aggregation; 1 also showed inhibition against thrombin-induced platelet aggregation.