bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevention of paracetamol‐induced hepatic damage in rats by picroliv, the standardized active fraction from Picrorhiza kurroa
Authors: Dwivedi Yogesh , Rastogi Ravi , Garg N. K. , Dhawan B. N.
Published: October 2006

Single oral administration of paracetamol (2 g/kg body wt) to rats caused significant changes in the activities of γ‐glutamyl transpeptidase, 5′‐nucleotidase, succinate dehydrogenase, glucose‐6‐phosphatase and cytochrome P450 and contents of glycogen and cholesterol in liver after 24 and 48 h. Total lipids and lipid peroxides in liver increased both at 24 and 48 h while protein content of liver decreased after 48 h. Levels of transaminases, alkaline phosphatase and bilirubin in serum also increased. The magnitude of these changes was more after 48 h of paracetamol administration. Picroliv, the iridoid glycoside fraction of Picrorhiza kurroa, when given orally to rats (6 and 12 mg/kg body wt for 7 days) caused significant reversal of the paracetamol‐induced biochemical changes. The degree of protection at the two doses of picroliv was almost similar.
Antifungal flavonoids from Varthemia iphionoides
Authors: Afifi F. Ü. , Al‐Khalil S. , Abdul‐Haq B. K. , Mahasneh A. , Al‐Eisawi D. M. , Sharaf M. , Wong L. K. , Schiff P. L.
Published: October 2006

Four flavonoids 5,7,4′‐trihydroxy‐3,3′‐dimethoxyflavone (3′,3′‐di‐O‐methylquercetin) (1), 5,4′‐dihydroxy‐3,7‐dimethoxyflavone (kumatakenin) (2), 5,4′‐dihydroxy‐6,7,8,‐trimethoxyflavone (xanthomicrol) (3) and 5,7,4′‐trihydroxy‐3,6,3′‐trimethoxyflavone (jaceidine) (4) were isolated and identified from the Jordanian Varthemia iphionoides. They have not previously been reported in this genus. The aqueous alkaline solution of these compounds showed little or no activity against the bacteria Staphylococcus aureus, Bacillus cereus and Salmonella typhimurium. Compound 2 was active against the fungi Fusarium solani and Candida tropicalis while compounds 1 and 3 were much more active against F. solani, Aspergillus parasiticus and C. tropicalis.
Assessment of the hypnotic/sedative effects and toxicity of Passiflora edulis aqueous extract in rodents and humans
Authors: Maluf E. , Barros H. M. T. , Frochtengarten M. L. , Benti R. , Leite J. R.
Published: October 2006

Passiflora species are used in folk medicine as hypnotic and sedative treatments. In this study the hypnotic‐sedative effects and toxicity of Passiflora edulis were assessed in rats and mice and in healthy volunteers. It was verified that some samples of Passiflora edulis had a nonspecific central nervous system depressant effect. Furthermore, hepatobiliary and pancreatic toxicity to animals and humans were detected.
Antiimplantation mechanism of action of embelin in rats
Authors: Prakash Anand O. , Sisodia Bhavna , Mathur R.
Published: October 2006

The antiimplantation mechanism of action of embelin has been studied in rats. Its administration caused a significant reduction in ovarian and uterine wet weight. Ovarian histology revealed newly formed corpora lutea and the biochemical constituents were decreased. Similarly, the uterus of pregnant treated rats did not show any preparative changes, decidualization, apposition reaction, stimulation or proliferation. Biochemical constituents also behaved as those of cyclic rats even on the day of implantation. These findings suggest that the administration of embelin to pregnant rats keeps the ovary and uterus in a cyclic condition.
Inhibition of ethyl phenylpropiolate‐induced rat ear oedema by compounds isolated from Ipomoea pes‐caprae (L.) R. Br.
Authors: Pongprayoon U. , Bohlin L. , Baeckström P. , Jacobsson U. , Lindström M.
Published: October 2006

The extract (IPA) of leaves from Ipomoea pes‐caprae (L.) R. Br. has previously been shown to reduce the development of rat ear oedema induced by ethyl phenylpropiolate (EPP) in a dose‐dependent manner. Using this bioassay to guide fractionation of the extract, two diastereomeric compounds, the actinidols 1a and 1b, were isolated (0.8% of IPA). The actinidols constitute part of the active principle of IPA. Compounds, previously isolated from IPA, with either prostaglandin synthesis inhibiting activity in vitro [2‐hydroxy‐4,4,7‐trimethyl‐1(4H)‐naphthalenone, (−)‐mellein and eugenol] or antispasmodic activity (E‐phytol) were also assayed for inhibitory effects on the development of EPP‐induced rat ear oedema. They all reduced oedema formation dose‐dependently. The results suggest that IPA consists of several active compounds which interfere with the process of inflammation in different ways.
Inhibitory effects of indonesian plant extracts on reverse transcriptase of an RNA Tumour Virus (I)
Authors: Kusumoto I. T. , Shimada I. , Kakiuchi N. , Hattori M. , Namba T. , Supriyatna S.
Published: October 2006

Methanol and water extracts of 30 Indonesian medicinal plants were tested for inhibitory activity on avian myeloblastosis virus (AMV)‐reverse transcriptase (RT). The most potent inhibition was shown by extracts of Loranthus parasiticus (whole plant), Helicteres isora (fruit), Terminalia belerica (fruit peel), Strobilanthes crispus (leaves) and Woodfordia floribunda (flower and leaves). Two kinds of template‐primers, (rA)n‐(dT)12–18 and (rC)n‐(dG)12–18 were examined for polymerization reaction but the inhibitory activity was stronger in the (rC)n‐(dG)12–18 directed reaction in most of the samples. These extracts showed no appreciable cytotoxicity at concentrations where over 90% of RT activity was inhibited.
Bioactivity screenings of plants selected on the basis of folkloric use or presence of lignans in a family
Authors: Richardson M. D. , Peterson J. R. , Clark A. M.
Published: October 2006

Twenty‐one plant species were selected to provide samples for a pilot test of the newly established in‐house antiviral screening programme at The University of Mississippi. These species were selected on the basis of folkloric use or the present of lignans in the plant family to increase the likelihood of positive results. The percentage (19%) of species showing antiviral activity against either Rhino virus 1A or Herpes Simplex virus 1 was within the percentage range of plants with antiviral activity found in other screenings for which a similar basis for collection was used. The plant extracts were also screened for antimicrobial activity and for toxicity to brine shrimp. Results of the screenings for all biological activities were correlated with the basis for collection. The best correlation between basis for collection and biological activity was seen for species from plant families containing lignans that were collected based on folkloric use for colds and anti‐Rhino viral activity.
Effects of aqueous extract of Baphia nitida on isolated cardiac tissues
Authors: Adeyemi O. O.
Published: October 2006

The pharmacological action of cold aqueous extract of fresh leaves of Baphia nitida was studied on cardiac preparations. The extract (5.0 × 10−3 g mL) reduced the rate and force of contraction of the isolated rabbit heart. The rate and force of contraction of the spontaneously beating rat atria was dose‐dependently reduced by 5.0 × 10−4 to 2.5 × 10−2 g/mL of the extract and this effect was not antagonized by 3.45 × 10−7 M atropine. The extract (5.0 × 10−2 g mL) completely blocked the positive chronotropic and inotropic effects of 10 mM CaCI2 but only reduced that of 1.61 × 10−7 M isoprenaline. The effect of the extract on CaCI2‐induced responses of the rat atria was not affected by 3 × 10−7 M propranolol. The use of this extract for treating palpitation locally may be related to its negative chronotropic and inotropic effects.
Evaluation of the silymarin content in Silybum marianum (L.) Gaertn. Cultivated under different agricultural conditions
Authors: Hammouda F. M. , Ismail S. I. , Hassan N. M. , Zaki A. K. , Kamel A. , Rimpler H.
Published: October 2006

An HPLC assay for the determination of silymarin in the fruits of Silybum marianum is given. The effect of different water regimes and nitrogen fertilization levels on the silymarin content of cultivated plants grown in reclaimed desert land have been studied. The highest silymarin contents were obtained upon nitrogen fertilization with 100, 150 kg/feddan (1 feddan = 4200 m2) and a 60% water regime without fertilization compared to the content of silymarin in wild plants.
The influence of Zea mays on urinary risk factors for kidney stones in rats
Authors: Grases F. , March J. G. , Ramis M. , Costa‐Bauzá A.
Published: October 2006

The effects on the calcium oxalate urolithiasis urinary risk factors of Zea mays (stigmata maidis), in herb infusion form, combined with different diets (standard, high glucidic, high protein) have beer studied using male Wistar rats. From the reported study, the possible antilithiasic effects of Zea mais infusion can be exclusively assigned to some diuretic activity. Thus, no influence on important urinary risk factors such as citraturia, calciuria or urinary pH values was detected. It is interesting to emphasize that the diuretic effect of the herb infusion was clearly dependent on the diet and was maximum when the rats were fed with the standard one.
Effect of some bisbenzylisoquinoline alkaloids on American Leishmania sp. in BALB/c mice
Authors: Fournet Alain , Barrios Alcira Angelo , Muñoz Victoria , Hocquemiller Reynald , Cavé André
Published: October 2006

Four bisbenzylisoquinoline alkaloids, antioquine, berbamine, gyrocarpine and isotetrandrine were tested in BALB/c mice infected with Leishmania amazonensis (IFLA/BR/67/PH8 or MHOM/GF/84/CAY‐H‐142) or L. venezuelensis (VE/74/PM‐H3). The treatments were initiated 1 day after the parasitic infection, with alkaloid at 100 mg/kg/day for 14 days and the reference compound, meglumine antimonate (GlucantimeR) at 200 mg/kg/day. Antioquine, berbamine and gyrocarpine were less potent than Glucantime against L. amazonensis (PH8). Only isotetrandrine exhibited activity approximately equal to or greater than Glucantime in BALB/c mice infected with L. amazonensis (PH8 or H‐142) and showed significant activity against L. venezuelensis. Experiments with a single local treatment on the footpad, 2 weeks after parasitic infection with L. amazonensis (PH8), showed that isotetrandrine at 200 mg/kg was less active than Glucantime at 400 mg/kg.
Analgesic and antiinflammatory properties of Scoparia dulcis L. Extracts and glutinol in rodents
Authors: De Farias Freire Sonia Maria , Da Silva Emim José Artur , Lapa Antonio José , Souccar Caden , Torres Luce Maria Brandão
Published: October 2006

The analgesic, antiinflammatory and antipyretic activities of the water (WE) and ethanolic (EE) extracts of Scoparia dulcis L. were tested in mice and rats. Both extracts (0.5 and 1 g/kg) p.o., prolonged the sleeping time induced by pentobarbital in mice, EE being more active than WE. Injections of EE (0.5–2 mg/kg i.v.) to anaesthetized rats induced a dose‐related hypertension inhibited by alpha‐blocker drugs; the hypertension was not obtained after oral treatment. EE (0.25‐1 g/kg p.o.) but not WE, reduced writhings induced by acetic acid in mice. Glutinol (30 mg/kg p.o.), a major triterpene obtained from EE, produced the same effect. The tail flick response of mice was not influenced by either extract. EE (0.5 and 1 g/kg) and glutinol (30 mg/kg) p.o., reduced the paw oedema and pleurisy induced by carrageenin in rats, but only EE (1 g/kg) reduced the paw oedema induced by dextran or histamine. No effect of EE was detected on chronic inflammation induced by cotton pellets and in yeast‐induced hyperthermia in rats. The results indicate that the extract of S. dulcis is endowed with analgesic effects probably related to the antiinflammatory activity of the plant. Those effects are related mainly to the presence of glutinol and flavonoids, which exert their action on the early phase of the acute inflammatory process.
Histomorphological and biochemical changes of lung tissues following capsaicin treatment in the rat
Authors: Mandal T. K. , De A. K. , Ghosh J. J.
Published: October 2006

Gross histomorphological alterations and biochemical changes, particularly in the lipid pattern of lung alveolar tissues, were oblerved in rats after intraperitoneal injection of capsaicin (the pungent principle of red hot pepper). Preliminary experiments showed that short‐term capsaicin treatment produced and inflammatory response with significant degenerative changes in the alveolar epithelial cells and increased cellularity of lung alveoli, as revealed by thickening of lung alveolar cells with occasional rupture of lung alveolar cellular integrity. The cytological changes were correlated with concomitant biochemical changes revealed by the decreased cholesterol and phospholipid content of lung alveolar tissues and infiltration of phospholipids towards the lumen of the alveoli which may be the cause of thickening of the alveoli cell lining of the lung tissues. On the other hand, long term capsaicin‐treated rat lungs showed a significant inhibition of capsaicin induced damage of lung tissues indicating a possible dual action of capsaicin on antiinflammatory respones in the pulmonary system.
Antipsychotic effects and tolerance of crude Rauvolfia vomitoria in Nigerian psychiatric inpatients
Authors: Obembe A. , Sokomba E. N. , Sijuwola O. A. , Olorunfemi P. O. , Alemika T. O. E. , Isichei C. O. , Ogunkeye O. O. , Bangudu A. B.
Published: October 2006

The dried root of Rauvolfia vomitoria administered orally to 10 psychiatric patients at doses up to 800 mg/day, in divided doses, showed antipsychotic effects. The overall side effects were minimal, without serious incidence of extrapyramidal symptoms. Physical examination and laboratory parameters tend to correlate with the theory that Rauvolfia vomitoria accumulates in the plasma. The antipsychotic effects of Rauvolfia vomitoria were shown to be dose dependent when given three‐times a day, with minimal side effects.
Effects of compounds of plant origin on the mutagenicity and metabolism of the tobacco‐specific nitrosamine NNK
Authors: Miller C. H. , Hamilton S. M. , Teel R. W.
Published: October 2006

We have investigated the effects of five phytochemicals on the microsomal‐dependent mutagenicity and metabolism of the tobacco‐specific nitrosamine, 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK). Two compounds, d‐limonene and silymarin, had no effect on NNK‐induced mutagenesis in Salmonella typhimurium TA1535 over the concentration range of 0.1–0.4 μmol/plate. Diallyl sulphide was weakly antimutagenic at a concentration of 0.4 μmol/plate. Both capsaicin and tannic acid showed a dose‐dependent inhibition of mutagenesis in TA1535. Metabolism studies using [3H]NNK indicated that the effects of the phytochemicals on NNK‐induced mutagenesis did not always correlate with the effects on NNK metabolism. α‐Carbon hydroxylation reactions are considered the most significant pathways involved in the metabolic activation of NNK to mutagenic and carcinogenic species. D‐Limonene and silymarin (0,4 μmol) had the least inhibitory effect on the total α‐carbon hydroxylation reactions, 19% and 28%. Capsaicin and diallyl sulphide inhibited these pathways by 74% and 70%. Tannic acid, the most potent phytochemical tested in this study, inhibited total α‐carbon hydroxylation pathways by 99%.
Inhibitory activity of extracts of Alternanthera brasiliana (amaranthaceae) against the herpes simplex virus
Authors: Lagrota M. H. C. , Wigg M. D. , Santos M. M. G. , Miranda M. M. F. S. , Camara F. P. , Couceiro J. N. S. S. , Costa S. S.
Published: October 2006

Five extracts from A. brasiliana, obtained through different procedures, showed anti‐HSV activity. The best activity was detected in a fraction (B) that was obtained from the crude cold aqueous extract on Sephadex G15. Fraction B showed low cellular toxicity and inhibition from 32.4% to 99.9% at concentrations from 6.2 to 50.0 μg/mL, exhibiting a therapeutic index of 32. Fractions obtained on Sephadex G100 and reversed‐phase column also showed considerable inhibition. Fraction B did not show any virucidal activity, however, its inhibitory activity was revealed during the later stages of the virus replication cycle. This fraction showed activity on DNA synthesis of infected cells.
Antiurolithiatic activity of lupeol, the active constituent isolated from Crateva nurvala
Authors: Anand R. , Patnaik G. K. , Kulshreshtha D. K. , Dhawan B. N.
Published: October 2006

In the traditional Indian system of medicine Crateva nurvala (Hindi: Varuna) constitutes a major ingredient of formulations used to treat urinary disorders including urolithiasis. In an earlier study we confirmed the antiurolithiatic activity in the crude extract of the plant, and further fractionation led to the isolation of the active constituent lupeol (Lup‐20(29)‐en‐3β‐ol). Antiurolithiatic activity of lupeol was assessed in rats by observing the weight of the stone, biochemical analysis of serum and urine, and histopathology of bladder and kidney. Lupeol not only prevented the formation of vesical calculi but also reduced the size of the preformed stones.
Antiprotozoal activities of Centipeda minima
Authors: Yu H. W. , Wright C. W. , Cai Y. , Yang S. L. , Phillipson J. D. , Kirby G. C. , Warhurst D. C.
Published: October 2006

In vitro activity against Giardia intestinalis was used for bioassay‐guided fractionation of crude extracts from C. minima. The sesquiterpene lactone, brevilin A was isolated and found to have antigiardial activity (IC50 = 16.1 μM) and was similarly active in vitro against Entamoeba histolytica (IC50 between 4.5 and 9 μM) and against Plasmodium falciparum (IC50 = 9.42 μM). Three flavonoids, quercetin, quercetin 3‐methyl ether and kaempferol 7‐glucosylrhamnoside were also isolated.
Effects of glycowithanolides from Withania somnifera on morphine‐induced inhibition of intestinal motility and tolerance to analgesia in mice
Authors: Ramarao P. , Rao K. T. , Srivastava R. S. , Ghosal S.
Published: October 2006

Effects of glycowithanolides (Ws, 10–150 mg/kg, i.p.), consisting of sitoindosides VII‐X, in combination with withaferin‐A, from Withania somnifera, in Swiss mice were evaluated on (i) morphine‐induced inhibition of gastrointestinal tract (GIT) transit and (ii) development of tolerance to morphine‐induced analgesia. Pretreatment with Ws significantly reversed the morphine (5 mg/kg, s.c.)‐induced inhibition of GIT transit at all doses. Ws (100 mg/kg, i.p., o.d., for 10 days) significantly inhibited the development of tolerance to morphine‐induced analgesia. Ws per se did not influence the intestinal motility nor did it produce any perceptible analgesic effect. The present and earlier findings with Ws suggest its potential in alleviating the adverse effects of morphine and the attendant immunodepression.
In vitro antimycotic activity of some natural products against Saprolegnia ferax
Authors: Perrucci S. , Cecchini S. , Pretti C. , Cognetti A. M. Varriale , Macchioni G. , Flamini G. , Cioni P. L.
Published: October 2006

During the in vitro screening of four essential oils and six substances of vegetable origin against the test fungi Saprolegnia ferax, thyme and savory essential oils, carvacrol and thymol exhibited the best antifungal activity at the lower concentrations. The antimycotic activity of malachite green, formalin and sodium chloride was also tested.
Spasmolytic action of the essential oil of Achillea ageratum L. in rats
Authors: de la Puerta R. , Herrera M. D.
Published: October 2006

The spasmolytic activity of Achillea ageratum L. essential oil in isolated rat duodenum has been in estigated. The essential oil was found to present a marked spasmolytic activity against acetylcholine and BaCl2 via a non‐competitive type of antagonism.
Cucurbitacins and their pharmacological effects
Authors: Miró M.
Published: October 2006

The cucurbitacins are triterpenic plant principles with varied pharmacological activities, found in several botanical families. This review includes the structures described in the literature, the plant‐containing cucurbitacins and their main pharmacological effects.
Antitumour potential of pollen extract on lewis lung carcinoma implanted intraperitoneally in syngeneic mice
Authors: Furusawa E. , Chou S. C. , Hirazumi A. , Melera A.
Published: October 2006

A defined pollen extract of selected plants has been reported to possess some pharmacological activities on chronic prostatis or benign prostatic hyperplasia. This paper describes the antitumour potential of the water soluble fraction (Cernitin T60) of pollen extract against Lewis lung carcinoma implanted intraperitoneally in syngeneic mice. Cernitin T60 was not cytotoxic in cell cultures at concentrations up to 2.5 mg/mL, while it is significantly prolonged the life‐span of mice carrying the tumour without any apparent side effects at 0.5 g/kg. In addition, Cernitin T60 demonstrated beneficial therapeutic effects in an additive fashion on the life‐span of mice when it was combined with standard cytotoxic antitumour drugs such as adriamycin, cisplatin, vincristine, methotrexate, fluorouracil, or thioguanine. The antitumour potential of Cernitin T60 was completely abolished by treatment with inhibitors of macrophage functions (2‐chloroadenosine or carrageenan), but not with a T‐cell inhibitor (cyclosporin A). Cernitin T60 appears to be a potent immunostimulator of macrophages.
Effect of buckwheat extract on free radical generation in rabbits administered high‐fat diet
Authors: Wójcicki J. , Samochowiec L. , Gonet B. , Juźwiak S. , Dabrowska‐Zamojcin E. , Katdońska M. , Tustanowski S.
Published: October 2006

In this study the effect of buckwheat extract (BE) on the level of malondialdehyde (MDA), lipids and hormones, and on the concentration of ascorbate free radicals in the liver (compared with rutin) in animals receiving a highfat diet (HFD) was measured. Male mongrel rabbits were randomly divided Into four groups: (1) control, (2) animals given HFD containing cholesterol and coconut oil, (3) rabbits treated with HFD + BE, (4) HFD + rufin, over a period of 12 weeks. The concentration of MDA in rabbits of group 3 (HFD + BE) was slightly but significantly decreased, whilst the number of ascorbate free radicals, examined in vitro, in the liver was markedly elevated. The level of testosterone in rabbit blood serum (group 3) was increased, but the insulin concentration was significantly diminished (in comparison with group 2). The content of total cholesterol and triglyceride in the liver of animals maintained on BE was decreased. Quite distinct superiority of BE, compared with rutin, was shown.
Active constituents of the bulbs of Fritillaria ebeiensis and their antitumour activity in mice
Authors: Ping Li , Guojun Xu , Luoshan Xu , Yixian Wang
Published: October 2006

The crude alkaloid of Fritillaria ebeiensis G. D. Yu et G. Q. Ji, administrated orally at a given dose, showed strong antitumour activity in inhibiting the growth of the solid type of hepatoma in mice. Chemical studies revealed that the active principles in this crude drug were verticine, verticinone and ebeiedine obtained from this species for the first time. This paper deals with the isolation and activity of these principles.
Acteoside: A new antihypertensive drug
Authors: Ahmad Mansoor , Rizwani Ghazala H. , Aftab Khalid , Ahmad Viqar Uddin , Gilani Anwarul Hasan , Ahmad Shahida Perveen
Published: October 2006

Acteoside is a phenylpropanoid, reported as a chemical constituent from different plant species, and was isolated as a pure compound on RP‐HPLC from the violet flowers of Syringa vulgaris. On pharmacological evaluation this compound exhibited a dose‐dependent decrease in sytolic, diastolic and mean arterial blood pressure in normotensive pentothal anaesthetized rats. The median effective dose was 10 mg/kg and lasted for 2–3 min, whilst heart rate also decreased.
Effects of an aqueous extract of Terminalia arjuna on isolated rat atria and thoracic aorta
Authors: Karamsetty Mallikharjuna , Ferrie Thomas J. , Kane K. A. , Gray A. I.
Published: October 2006

Terminalia arjuna (Combretaceae) is used traditionally in ayurveda, to treat a variety of cardiovascular disorders. The aims of this study were to characterize the positive inotropic effect of the aqueous extract of T. arjuna bark in isolated paced rat left atria and to study its effects on a vascular smooth muscle preparation, the rat thoracic aorta. The crude and semipurified aqueous extracts produced a positive inotropic effect of rat atria and the maximum contraction was comparable to that produced by isoprenaline. The positive inotropic effect of the extract was completely blocked by a β‐adrenoceptor blocker, propranolol, and an uptake‐1 blocker, cocaine. In precontracted aorta, the aqueous extract produced a contraction followed by relaxation. Propranolol did not block the relaxant effect of the aqueous extract. It is concluded that the positive inotropic effect of the aqueous extract was mediated via an action on β1‐adrenoceptors and was likely to be due to the release of noradrenaline from the sympathetic nerve endings. The vasorelaxant effect of the extract, however, was not mediated via an action on β2 adrenoceptor.
Further antibacterial diterpenes from the bark and leaves of Juniperus procera hochst. ex Endl
Authors: Muhammad Ilias , Mossa Jaber S. , Al‐Yahya Mohammed A. , Ramadan Ahmed F. , El‐Feraly Farouk S.
Published: October 2006

The bark of Juniperus procera yielded three antibacterial diterpenoids, (+)‐E‐communic acid (1), (+)‐Z‐communic acid (2) and (+)‐totarol (3). Compound 2 exhibited significant activity against Gram‐positive bacteria, while 1 was found to be less active. Compound 3, on the other hand, demonstrated potent activity against Mycobacterium organisms, while its corresponding 3β‐hydroxy‐derivative 4 was found to be inactive. The chromatographic separation of (+)‐Z‐communic acid (2) from (+)‐E‐communic acid (1) and those previously unreported spectral data of 1 and 2 are described. In addition, the leaves yielded (+)‐8α‐acetoxyelemol, β‐peltatin A methyl ether and deoxypodophyllotoxin.
The Measurement of Partition Coefficients
Authors: Dearden John C. , Bresnen Gaynor M.
Published: October 2006

Partition coefficient (P) is a widely‐measured property, yet there is considerable variation among published log P values. This paper examines the factors that can affect the measurement of partition coefficient, and makes recommendations as to good practice. Accuracy of partition coefficient determination can be affected by temperature, lack of mutual phase saturation, pH, buffer type and concentration, phase miscibility, solute concentration, solute and solvent purity, solute stability, phase volume ratio, solute adsorption and failure to reach equilibrium conditions. It is recommended that partitioning be carried out at constant temperature using either a stirred flask technique or the filter probe.
The Relationship Between Chemical Structure and the Logarithm of the Partition Coefficient
Authors: Koehler M. G. , Grigoras Stelian , Dunn W. J.
Published: October 2006

The relationship between chemical structure of a solute and the logarithm of its partition coefficient (log P) between the aqueous and a nonpolar phase is poorly understood. We have recently shown that the variation in log P data for 50 low molecular‐weight organic solutes in 6 aqueous‐non‐polar solvents is a function of two structural features. The main feature accounts for ≈︁60% of the variation in the log P data, and is uniformly weighted in all 6 nonpolar solvent systems. This suggests that it is related to the aqueous solution properties of the solute. The first feature is termed the isotropic surface area, or the surface area associated with the nonpolar portion of the solute when the solute is considered to be a hydrated complex. The hydrated solute complex is termed a supermolecule with waters of hydration occupying hydrogen bonding sites on the functional groups of the solute. Empirical rules for formation of the super molecule are discussed.

In this report the analysis is extended to log P data for 72 solutes in the 6 nonpolar solvent systems. The results of the analysis are essentially unchanged for this more extended data set and the second factor is tentatively identified. The second structural feature accounted for ≈︁35% of the variation in the log P data was not equally weighted in all solvents and is difficult to interpret structurally.
Model Solvent Systems for QSAR Part I. Propylene Glycol Dipelargonate (PGDP). A new Standard Solvent for use in Partition Coefficient Determination
Authors: Leahy David E. , Taylor Peter J. , Wait Alan R.
Published: October 2006

Data for 216 partition coefficients in propylene glycol dipelargonate (PGDP) are given, along with 80 derived fragment values and a scheme for calculating the p.e. 2 correction from which many more log P values can be derived. PGDP log P and f‐values are contrasted with those of octanol and discussed in terms of the differing balance of proton donor/acceptor properties which these solvents show. It is suggested that PGDP, in conjunction with octanol, can be used as a model solvent probe for membrane binding and transport characteristics in ways that may have special relevance to biological selectivity.
A Pharmacophore Hypothesis for Antidepressant Activity: Accomodation of Viloxazine
Authors: Brown George R.
Published: October 2006

In a previous study of the conformation‐activity relationships of antidepressant drugs a pharmacophore hypothesis was developed. This report shows that an incorrect structure of viloxazine was used to validate the hypothesis and comments on the relevance of the fit of the correct structure of viloxazine to the pharmacophore.
Corchop – an Interactive Routine for the Dimension Reduction of Large QSAR Data Sets
Authors: Livingstone David J. , Rahr Elizabeth
Published: October 2006

The combination of the techniques of QSAR and Computer Chemistry (Quantum and Molecular Mechanics) has led to the generation of very large data sets, in terms of the number of parameters used to characterise the molecules of interest. Although there are techniques which may be used to analyse such data sets, it is recognised that there is considerable redundancy within these data. The computer routine CORCHOP was devised to aid the systematic reduction of such data sets to provide a parsimonius description whilst retaining their intrinsic information content. The use of this technique is illustrated by an example data set of antibacterial quinolones.
Drug Lipophilicity in QSAR Practice: I. A Comparison of Experimental with Calculative Approaches
Authors: Mannhold Raimund , Dross Karl P. , Rekker Roelof F.
Published: October 2006

Experimental and calculated data of drug lipophilicity, i.e. octanol/water partition coefficients (log Pobs) and hydrophobic fragmental constants (Σf, C log P) have been compared for the following four groups of drugs: antiarrhythmics (AA), β‐blockers (BB), phenothiazines (PT) and benzamides (BA).

Measured log P values indicate significantly varying lipophilicity ranges in the case of these four groups (AA>BB>BA>PT).

Comparison of the two calculative approaches with observed log P values yields almost identical qualities. Strongest discrepancies between calculative and experimental data are discussed on the basis of putative experimental pitfalls or in relation to structurally derived miscalculations.
The Electrotopological State: An Atom Index for QSAR
Authors: Hall Lowell H. , Mohney Brian , Kier Lemont B.
Published: October 2006

A new characterization of atoms in molecules is introduced as the electrotopological state index, which combines both the electronic character and the topological environment of each skeletal atom in a molecule. The electrotopological state (E‐state) of a skeletal atom is formulated as an intrinsic value Ii plus a perturbation term ΔIi, arising from the electronic interaction within the molecular topological environment of each atom in the molecule. The atom intrinsic value, for first row atoms, is expressed as I = (δv + 1)δ, in which δv and δ are the counts of valence and sigma electrons, respectively, for the atom in the molecular skeleton. The E‐state, Si, for atom i is defined as Si = Ij + ΔIj, where the influence of other atoms on atom i, ΔIi, is given as Σ(Ij — Ij)/rij2; rij is the graph separation between atoms i and j, counted as number of atoms, including i and j. Information in the electrotopological state is revealed by examples of various types of organic structures, including skeletal branching and heteroatom variation. The relation of the E‐state value to NMR chemical shift is demonstrated for a series of carbonyl compounds. QSAR examples are given for hydrazide inhibition of MAO and for receptor binding of β‐carbolines. These examples reveal the power of this approach to QSAR using atom level indexes, computed directly from molecule connection tables, in which it is possible to identify atoms and regions in the molecule which are important for activity.
The EDISFAR Programs. Rational Drug Series Design
Authors: Pastor M. , Alvarez‐Buiila J.
Published: October 2006

The computer package EDISFAR is described. The programs can manage physico‐chemical information from a database (MONOBASE) of the fragment parameters classically used in drug design, providing assistance in the use of the techniques related with the Hansch‐Fujita analysis. The user can make design of exploring series of bioactive compounds, using a great variety of techniques, and once a QSAR model has been obtained, can calculate optimum derivatives using the parameters of the MONOBASE. The program has been designed emphasizing its flexibility, accessibility by the practical chemist, and compatibility with other statistics programs or computers.
Structure‐Toxicity Relationships for α, β‐Unsaturated Alcohols in Fish
Authors: Mekenyan Ovanes G. , Veith Gilman D. , Bradbury Steven P. , Russom Christine L.
Published: October 2006

Previous toxicity testing with fathead minnows (Pimephales promelas) indicated that some unsaturated acetylenic and allylic alcohols can be metabolically activated, via alcohol dehydrogenase, to highly toxic α, β‐unsaturated aldehydes and ketones or allene derivatives. Although several in vivo and in vitro toxicological and biochemical endpoints can differentiate these alcohols by toxic mechanism, the use of stereoelectronic molecular descriptors to discriminate these toxicants, and subsequently to predict potency, had not been previously attempted. Exploration of several descriptors indicated that soft electrophilic characteristics of acetylenic or allylic moieties in the suspected metabolites unambiguously discriminated reactive and narcotic toxicants. The acute toxicity of alcohols acting as narcotics was accurately predicted using an existing quantitative structure‐activity relationship for nonpolar narcosis. The toxicity of alcohols mediated by metabolic activation was estimated quantitatively using acceptor superdelocalizability of specific carbon atoms of the acetylenic or allylic moiety in the putative electrophilic intermediates.
A Rigorous Test for SPARC's Chemical Reactivity Models: Estimation of More Than 4300 Ionization pKas
Authors: Hilal S. H. , Karickhoff S. W. , Carreira L. A.
Published: October 2006

Ionization pKas for a large set of molecules were calculated using reactivity models developed in the computer program SPARC. SPARC uses relatively simple computational algorithms based on fundamental chemical structure theory to estimate ionization pKas of organic molecules strictly from molecular structure. Molecular structures are broken at each essential single bond into functional units with intrinsic properties. Reaction centers (acid or base) are identified and the impact of appended molecular structure on ionization pKa is quantified by perturbation theory. Resonance, electrostatic, solvation and H‐bonding models have been developed and tested on 4338 pKas for 3685 compounds. The RMS deviation for the acids and the amino reaction center was 0.36 pKa units whereas that for the in‐ring N and = N reaction centers was 0.41. Microscopic ionization constants, zwitterionic constants, isoelectric points, and molecular speciation as a function of pH can be calculated using the SPARC models.
QSAR for Allergic Contact Dermatitis
Authors: Graham Cynthia , Gealy Robert , Macina Orest T. , Karol Meryl H. , Rosenkranz Herbert S.
Published: October 2006

Allergic contact dermatitis (ACD) is a widespread concern in which sensitization occurs to low molecular weight chemicals. Currently, animal and human assays are used to identify chemicals with potential to cause ACD. MultiCASE, a computer based structure‐activity relational system was employed to evaluate a data base of contact sensitizers and identify structural determinants (biophores) associated with sensitization. The data base was derived from reports of animal and human studies and consisted of 1034 chemicals of which 317 were classified as sensitizers (extreme, strong, moderate, or weak), 22 chemicals had marginal (questionable) activity, and 695 were inactive. MultiCASE identified 49 biophores with related expanded fragments which accounted for the activity of all active chemicals. The major biophores consisted of: 1) a nitrogen double‐bonded to a carbon or a nitrogen; 2) substituted aromatic structures; 3) thiol and disulfide containing fragments; and 4) electrophilic moieties. Modulators of each biophore, which either augmented or decreased potency, included additional structural fragments, two dimensional distance descriptors, as well as physico‐chemical characteristics. Internal evaluation of the data base indicated the sensitivity was 99.6%, and the specificity of the data set was 99.4%. Prediction of the activity of chemicals not in the learning set gave a concordance of 90.2% with experimental results. These findings demonstrate the ability of MultiCASE to identify contact sensitizers and suggest its ability to screen chemicals for their potential to produce ACD.
Calculation Procedures for Molecular Lipophilicity: a Comparative Study
Authors: Mannhold Raimund , Dross Karl
Published: October 2006

The predictive power of 14 calculation procedures for molecular lipophilicity is checked by comparing with reliable experimental log P values from the literature. The database of 138 test compounds comprises 90 simple organic structures and 48 chemically heterogeneous drug molecules (β‐blockers, class I antiarrhythmics and neuroleptics).

The present investigations lead us to conclude that the predictive power of the calculation procedures is significantly better for simple organic molecules than for chemically heterogeneous drug structures. The calculation procedures should be arranged in three groups with significantly differing predictive power: fragmental > atom‐based > conformation‐dependent approaches.
Bringing science to life: A synthesis of the research evidence on the effects of context‐based and STS approaches to science teaching
Authors: Bennett Judith , Lubben Fred , Hogarth Sylvia
Published: October 2006

Context‐based and science–technology–society (STS) approaches to teaching science in high school have become widely used over the past two decades. They aspire to foster more positive attitudes to science while, at the same time, provide a sound basis of scientific understanding for further study. This paper reviews the detailed research evidence from 17 experimental studies undertaken in eight different countries on the effects of context‐based and STS approaches, drawing on the findings of two systematic reviews of the research literature. The review findings indicate that context‐based/STS approaches result in improvement in attitudes to science and that the understanding of scientific ideas developed is comparable to that of conventional approaches. The approaches also result in more positive attitudes to science in both girls and boys and reduce the gender differences in attitudes. The paper also considers issues emerging from work in the area in relation to study design and the constraints which may militate against the use of experimental research designs when gathering evidence of impact of interventions. A fundamental constraint is the extent to which it is possible to make comparisons between existing methods and interventions when the aims are overlapping but also differ in significant ways. © 2006 Wiley Periodicals, Inc. Sci Ed 91:347–370, 2007
Techniques to improve exploration efficiency of parallel self‐adaptive genetic algorithms by dispensing with iteration and synchronization
Authors: Takashima Eiichi , Murata Yoshihiro , Shibata Naoki , Ito Minoru
Published: October 2006

The exploration efficiency of GAs depends on parameter values such as the mutation rate and crossover rate. To save the labor of manually adjusting these values, GAs which automatically adjust parameters (adaptive GAs) have been proposed. However, most of the existing adaptive GAs can adjust only a few parameters simultaneously. Although several adaptive GAs can adjust many parameters simultaneously, these algorithms have a large computational cost.

In this paper, we propose the Self‐Adaptive Island GA (SAIGA) and its asynchronous implementation Asynchronous SAIGA (A‐SAIGA). These two GAs are combinations of Meta GA and Island GA, and can adapt many parameters simultaneously with a computational cost equivalent to that of the simple GA. A‐SAIGA improves exploration speed by avoiding synchronization between islands.

Throughout our evaluation experiments, we confirmed that the performance of these GAs is close to that of the simple GA with optimal parameters. We also confirmed that A‐SAIGA outperforms SAIGA in exploration speed. © 2006 Wiley Periodicals, Inc. Syst Comp Jpn, 37(14): 25–33, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.20635
Toxicity of azaarenes in bacterial assays: Mechanistic studies
Authors: Catallo W. James , Portier Ralph J. , Gale Robert J.
Published: October 2006

Exposure of bacterial cells to selected azaarenes causes respiratory inhibition, membrane damage, decreased cellular ATP synthesis, and decreased cell viability. The purpose of this work was to examine the chemical mechanisms of acute toxicity of azaarenes and provide a preliminary model of azaarene cellular effects. Results of bioassays and in vitro spectrochemical and electrochemical experiments suggest that azaarenes alter membranes and electron transfer (ET) molecular assemblies primarily through noncovalent interactions not involving organic or oxy free radicals. The data suggest that membranes and membrane‐linked systems are altered via azaarene‐mediated chelation of divalent cations (Ca and Mg) found in the lipopolysaccharide matrix of the bacterial outer membrane. This gives rise to altered structure/function of periplasmic and inner membrane systems, and may contribute to changes in ET. Electrochemical analyses indicate that azaarenes also change the redox chemistry of flavin centers and seem to increase the ease with which ET processes occur between biochemical electron donors (NADH) and tetrazolium acceptors (iodonitrotetrazolium).
Fate and toxicity assessment of linear alkylbenzene sulfonates in drinking water using the ames test
Authors: Romera J. , Ventura F. , Caixach J. , Rivera J. , Guerrero R.
Published: October 2006

The genotoxic activity of the methanolic water extracts of prechlorinated water from Barcelona (NE Spain) using the Ames test was studied. High performance liquid chromatography (HPLC) and mass spectrometry in the mass spectroscopy/fast atom bombardment mode (MS/FAB) was employed to tentatively identify organic compounds responsible of genotoxic activity.

Methanolic extracts of prechlorinated water were highly mutagenic in the Ames test, mainly with the TA98 strain for concentration lesser than 1 L. On the other hand, the TA100 strain showed higher mutagenicity for tap water extracts and concentrations higher than 1 L.

Also, a strong toxic effect was observed when methanolic extracts were analyzed by the Ames test. Toxicity showed a reduction of the genotoxic ratio by a characteristic negative slope for the concentration vs genotoxicity curve. Toxicity was usually observed using the TAlOO strain and at a higher concentration than mutagenicity does. Both mutagenicity and toxicity in the Ames test showed a characteristic pattern depending on their origin (tap or prechlorinated water).

It was possible to separate mutagenic from toxic fractions by HPLC. These subfractions were analyzed by MS/FAB in order to identify the organic compounds responsible for these effects, but unsuccessful results were obtained for mutagenic subfractions.

Alkylbenzenesulfonates (LA3) were the sole compounds identified in toxic subfractions. The correlation between toxicity of samples (TA100 strain) and the presence of LAS was proved by comparison of toxicity from a standard LAS and those observed from real samples. An EC 50 of 9.8 mg/L for LAS has been established by the Ames test using the TAlOO strain. © 1993 John Wiley & Sans, Inc.
Comparative assessment of the SOS Chromotest kit and the Mutatox test with the Salmonella plate incorporation (Ames test) and fluctuation tests for screening genotoxic agents
Authors: Legault R. , Blaise C. , Rokosh D. , Chong‐Kit R.
Published: October 2006

Genuine needs for rapid, simple, and cost‐efficient biotesting procedures to screen an ever‐increasing number of chemicals and environmental samples are making the search for such assays a constant endeavor. With respect to genotoxicity screening, we compared, in this study, the performance of two novel assays (Vibrio fischeri M169 Mutatox™ assay and the Escherichia coli PQ37 SOS Chromotest kit assay) with two well‐established Ames testing procedures (plate incorporation and fluctuation assays). Testing material included 14 chemicals (10 potentially directly acting and 4 indirectly acting compounds) reflecting different chemical classes (2 inorganics, 2 pesticides, 2 halogenated hydrocarbons, 2 alkylating agents, 2 aromatic amines, 1 chlorophenol, and 3 polycyclic aromatic hydrocarbons). Comparative assessment criteria included (1) interprocedural agreement in detecting presence or absence of genotoxicity, (2) accuracy in being able to recognize animal (non)carcinogens, and (3) sensitivity (detection of lowest actively genotoxic concentration). In terms of qualitative responses, both the SOS Chromotest (86% agreement) and Mutatox assays (93% agreement) were good predictors of the Ames testing mutagenicity. For their capability to correctly discriminate between (non)carcinogens, accuracy was 82% (9 of 11 chemicals) for Mutatox, 73% (8 of 11 chemicals) for Ames testing, and 64% (7 of 11 chemicals) for the SOS Chromotest. In general, the Salmonella‐based assays proved more sensitive (6 times out of 9 chemicals) than the Mutatox (3 times out of 9 chemicals) and the SOS Chromotest (never more sensitive). Overall, this study demonstrates reliable performances by both the SOS Chromotest and Mutatox for chemical genotoxicity screening when results are referenced to the well‐validated Ames assay. Although additional comparative data with other chemicals will be required, it appears likely that these more practical and cost‐efficient procedures can be presently useful to screen genotoxic activity of various xenobiotics and environmental samples. © 1994 by John Wiley & Sons, Inc..