A new neoquassin derivative from Quassia amara

A new quassinoid, a dihydronorneoquassin, has been isolated from Quassia amara wood. In addition the known compounds, paraine and isoparaine, were     

A New Bacillus pasteurii Urease Inhibitor from Euphorbia decipiens

Inhibition of Bacillus pasteurii urease enzyme by 3,7,15-tri-O-acetyl-5-O-nicotinoyl-13,14-dihydroxymyrsinol (1), a diterpene ester with a myrsinol-type skeleton, isolated from Euphorbia decipiens Boiss. & Buhse, was un-competitive consistent with the molecular docking results. The Ki value was 117.40 ± 0.7 μM.     

Growth of and quassin accumulation by cultures of Quassia amara

Callus and suspension cultures were established from Quassia amara, a member of the Simaroubaceae. Analysis of the tissue culture showed that quassin was present in both callus and suspension cultures. The effect of variation in auxin and cytokinins on both callus growth and the presence of quassin was examined. The suspension culture was grown in a 7 liter bioreactor when good yields of quassin were achieved.Abbreviations IAA indole-3-acetic acid - IBA indolebutyric acid - 2,4-D 2,4-dichlorophenoxyacetic acid - NAA naphthaleneacetic acid - 6BA 6-benzyladenine - IpA N⁶ (-isopentenyl) adenine - IpAR N⁶ ( isopentenyl) adenine riboside - td doubling time     

Westalsan: A New Acetylcholine Esterase Inhibitor from the Endophytic Fungus Westerdykella nigra

A new cytochalasan alkaloid, westalsan ( 1 ), along with two known cytochalasan compounds, phomacin B ( 2 ) and 19-hydroxy-19,20-dihydrophomacin C ( 3 ), were isolated from the solid rice culture of Westerdykella nigra, a marine-derived endophytic fungus, isolated from the roots of mangrove Avicennia marina (Forssk.) Vierh. The structures of compounds 1 – 3 were established on the basis of extensive 1D and 2D NMR spectroscopic techniques in combination with HR-ESI-MS. The ability of the isolated compounds to inhibit acetylcholine esterase activity was evaluated. Compound 3 showed the highest acetylcholine esterase inhibitory activity (IC₅₀ 0.056±0.003 μM), followed by compound 1 (IC₅₀ 0.088±0.005 μM) and compound 2 (IC₅₀ 0.140±0.007 μM) compared to donepezil (IC₅₀ 0.035±0.002 μM). This was further confirmed by molecular docking experiment.     

Raphanusol B: A Growth Inhibitor of Light-grown Radish Seedlings

A growth inhibitor, for which the name raphanusol B is proposed,was isolated in crystalline form from light-grown Sakurajimaradish seedlings and has been shown to be 1-sinapoylglucoseby spectrometric analysis. Raphanusol B inhibited the growthof intact and excised hypocotyls of etiolated radish seedlings.The raphanusol B content of the radish seedlings increased greatlyunder red light, but decreased in the dark. ¹Present address: Department of Chemistry, Faculty of Science,Kagoshima University, Korimoto 1, Kagoshima 890, Japan. (Received October 6, 1980; Accepted December 6, 1980)     

Germ Tube Growth Inhibitor from Cronartium comandrae Aeciospores

The reduction of nucleic acid by an endogenous polynucleotide phosphorylase and ribonuclease in cells of Brevibacterium JM98A (ATCC 29895) was studied. A simple process was developed for the activation of the endogenous RNA-degrading enzyme(s). RNA degradation was activated by the presence of Pi with 14.2 mumol of ribonucleoside 5'-monophosphate per g of cell mass accumulating extracellularly. The optimum pH for degradation of RNA was 10.5 and the optimum temperature was 55 to 60 degrees C. Enzymatic activity was inhibited by the presence of Ca2+, Zn2+, or Mg2+. Although some of the RNA-degrading enzymatic activity was associated with the ribosomal fraction, most was soluble. Both polynucleotide phosphorylase and ribonuclease activities were identified.     

A New VGLUT-Specific Potent Inhibitor: Pharmacophore of Brilliant Yellow

The increased concentration of glutamate in synaptic vesicles, mediated by the vesicular glutamate transporter (VGLUT), is an initial vital step in glutamate synaptic transmission. Evidence indicates that aberrant overexpression of VGLUT is involved in certain pathophysiologies of the central nervous system. VGLUT is subject to inhibition by various types of agents. The most potent VGLUT-specific inhibitor currently known is Trypan Blue, which is highly charged, hence membrane-impermeable. We have sought a potent, VGLUT-specific agent amenable to easy modification to a membrane-permeable analog. We provide evidence that Brilliant Yellow exhibits potent, VGLUT-specific inhibition, with a K_i value of 12 nM. Based upon structure–activity relationship studies and molecular modeling, we have defined the potent inhibitory pharmacophore of Brilliant Yellow. This study provides new insight into development of a membrane-permeable agent to lead to specific blockade, with high potency, of accumulation of glutamate into synaptic vesicles in neurons.     

A Germination Inhibitor from Sugar-Beet

There is present in the water extract of sugar-beet seed ballsan unsaturated yellow oil which is capable of inhibiting germinationof various seeds. It also inhibits salt uptake and the respirationof sugar-beet tissue disks. The activity of the polyphenolaseenzyme present in beet tissue is also depressed. The role ofthe oil in inhibition of sugar-beet germination is discussed.     

USF-19A,a New Lipoxygenase Inhibitor from Streptomyces sp.

USF-19A, a soybean Jipoxygenase (SBL) and human 5-lipoxygenase (5-LO) inhibitor, was isolated from Streptomyces sp. USF-19 strain. Its chemical structure was determined by spectroscopic evidence to be a new member of the antimycin antibiotic family. The IC₅₀ value of USF-19A against 5-LO was 28.0 μM.     

一种新的血管生成抑制因子--hPK-5

hPK-5是人纤溶酶原的结构域片段,它针对增生的内皮细胞而呈现很高的作用特异性,表现出抗内皮细胞增殖活性,调节血管增生的平衡以及炎症反应。鉴于它是内源性的抗血管生成因子,且具有分子量小、易于表达和高效的生物学活性等优势,充分展示了其重要的研究价值和临床应用前景。     

HCV治疗的新方法:RNA依赖的RNA聚合酶抑制剂

丙型肝炎病毒（hepatitis C virus,HCV）感染呈世界流行趋势,50%感染者转变为慢性肝炎,部分发展为肝硬化、肝细胞癌,给人类健康带来了极大危害.目前,没有疫苗研制成功,现有的HCV治疗药物普遍存在局限性,或者有一些药物没有发挥应有的作用.因此,开发新型、安全有效的抗HCV药物成为迫在眉睫的问题.NS5B蛋白是HCV复制的核心物质,具有RNA依赖的RNA聚合酶（RdRp）功能.研发有效的NS5B抑制剂,从而阻断病毒的复制,成为许多科研机构及制药公司的研究热点,有一些NS5B抑制剂已进入临床实验阶段.     

Action Potential in Luffa cylindlica and its Effects on Elongation Growth

The action potential of the non-seismonastic plant, Luffa cylindrica,was studied and characterized. Single action potentials of 30to 60 mV were evoked by electrical or cooling stimuli appliedto the stem internode. Action potentials were transmitted withoutdiminution along stimulated internodes shorter than 40 mm inlength. No difference in velocity between acropetal and basipetaltransmission was observed. This behavior is very similar tothat of Mimosa and Biophytum. The velocity of transmission ofaction potentials along internodes of Luffa was dependent upondistance from the point of stimulation; 10 to 20 mm sec^–1upto 40 mm, and 70 mm sec^–1 at around 50 mm from the pointof stimulation. The action potential was not transmitted tothe neighboring internode. Action potentials were also observedin the petiole and leaf. Beyond the threshold stimulus, theamplitude of the transmitted action potential depended on thestrength of the stimulus. The absolute and relative refractoryperiods for the transmission of action potentials were 2 minand 2 to 5 min, respectively. Elongation growth of the stem, recorded using a differentialtransformer, decreased after the generation of a single actionpotential in the upper most internode. This decreased growthrate continued for more than 5 min. (Received March 10, 1986; Accepted June 11, 1986)     

A Protease Inhibitor from Penicillium cyclopium

A protease inhibitor produced by Penicillium cyclopium on solid cultures of wheat bran was purified by means of column chromatography on Duolite A-2 and DEAE-cellulose, acetone precipitation and lyophilization. The purified inhibitor obtained as a white, floccose and hygroscopic substance was monodisperse by ultracentrifugal analysis. It was found to be an acidic macro-molecule of a molecular weight of about 5000. The chemical analyses rejected the possibility of the presence of amino acids, peptides, sugars, amino sugars, or uronic acids in the inhibitor molecule.

Properties of a protease inhibitor from Penicillium cyclopium were studied. The pH range of the inhibitor action is restricted to acid pH, optimally at pH 3. Increasing temperature accelerates its action upon enzyme. The inhibitor causes enzyme inactivation in proportion to its concentration. It is fairly stable in an acid solution but unstable in an alkaline solution. It undergoes destruction by heat, hydrogen peroxide and ascorbic acid. The inhibitor reversibly combines with Al³⁺, Fe³⁺, Ag⁺ and Cu²⁺ to produce a precipitate. Salts interfer with the inhibitor activity. Generally, acid proteases from various penicillia are susceptible to the inhibitor while those from other genera are resistant.     

A Protease Inhibitor from Penicillium cyclopium

When the protease inhibitor from Penicillium cyclopium was mixed with the acid protease of the mold at acid pH formed a precipitate consisting of a enzyme-inhibitor complex. The precipitation occurred maximally at pH 3.0 and was interfered with by increasing amounts of salts and other protein. Subsequent incubation of the complex brought about inactivation of the enzyme and the inactivation was found to be accompanied by modification of the enzyme so that less was precipitable with trichloroacetic acid. Paper chromatography revealed that the enzyme on complete inactivation had been degraded to several fragments or polypeptides. The inhibitor acted on the enzyme in a catalytic fashion, bringing about degradation of more than a stoichiometric amount of enzyme. The proposed mechanism of the inhibitor action involved acceleration of auto-digestion of the enzyme which splits the molecule into small fragments and abolishes the activity.     

New findings on Simalikalactone D, an antimalarial compound from Quassia amara L. (Simaroubaceae)

Quassia amara L. (Simaroubaceae) is a species widely used as tonic and is claimed to be an efficient antimalarial all over the Northern part of the Amazon basin. Quassinoid compound Simalikalactone D (SkD) has been shown to be one of the molecules responsible for the antiplasmodial activity of a watery preparation made out of juvenile fresh leaves of this plant. Because of its strong antimalarial activity, we decided to have a further insight of SkD pharmacological properties, alone or in association with classical antimalarials. At concentrations of up to 200μM, we showed herein that SkD did not exert any apoptotic or necrotic activities in vitro on lymphoblastic cells. However, an antiproliferative effect was evident at concentrations higher than 45nM. SkD was inefficient at inhibiting heme biomineralization and the new permeability pathways induced by the parasite in the host erythrocyte membrane. With respect to Plasmodium falciparum erythrocytic stages, SkD was almost inactive on earlier and later parasite stages, but potently active at the 30th h of parasite cycle when DNA replicates in mature trophozoites. In vitro combination studies with conventional antimalarial drugs showed that SkD synergizes with atovaquone (ATO). The activity of ATO on the Plasmodium mitochondrial membrane potential was enhanced by SkD, which on its own had a poor effect on this cellular parameter.     

Xanthoxin: A Growth Inhibitor in Light-grown Sunflower Seedlings, Helianthus annuus L.

Methanol extracts from light- and dark-grown sunflower seedlings,Helianthus annuus L., var. ‘Inra No. 6501’, weresubjected to solvent partition. The neutral diethyl ether fractionfrom the light-grown seedlings contained material(s) which inhibitedcress seed germination. Such inhibition was scarcely detectablein extracts of the etiolated seedlings. Sometimes inhibitionalso occurred in the petroleum spirit fraction. A mixture ofcis, trans- and trans, transxanthoxin showed the same partitioncharacteristics as the inhibiting substance(s); the latter co-chromatographedwith xanthoxin in all paper, thin layer, and high pressure liquidchromatography separation procedures tried. The inhibition wasalso detectable with the Avena colcoptile straight growth bioassay. It is concluded that xanthoxin is formed during illuminationof sunflower seedlings; its role in the phototropic responseof these seedlings is discussed.