Essential oils from two endemic species of Apiaceae from Iran

The composition of essential oils of Leutea glaucopruinosa (Rech.f.) Akhani & Salimian comb. nov., and Zeravschania (Boiss. & Hausskn.) Salimian & Akhani comb. nov. were analysed by GC-MS. 49 compounds are identified in the former and 33 compounds in the latter, comprising a total of 76 compounds in both species. Both species were originally described under Peucedanum, which are transferred in this paper into Leutea and Zeravschania, respectively. The chemical compounds of the essential oils show that there are only seven common compounds between two species. The major compounds of L. glaucopruinosa are mostly monoterpene hydrocarbons and oxygenated monoterpenes, in which alpha-pinene (31.5%), sabinene (9.7%), beta-pinene (9.2%), exo-fenchyl acetate (4.5%) are dominant. In Z. pastinacifolia sesquiterpene hydrocarbons and phenylpropanoids dominate with beta-bisabolene (37.3%), 3,1-butyl-1,2-dimethoxy benzene (14.9%), 10,11-dimethylbicyclo[6.3.0]undec-(8)-en-9-one (12.9%), 4-t-butyl-1,2-dimethoxy benzene (6.8%), (E)-asarone (5.1%) and elemicine (4.1%) as major compounds.     

Spindle disturbances in mammalian cells. III. Toxicity, c-mitosis and aneuploidy with 22 different compounds. Specific and unspecific mechanisms

Early investigations have shown that many chemically different compounds can cause disturbances of the spindle function (c-mitosis) in eukaryotic cells and that there is an unspecific (physical) mechanism based on the partitioning of the compound into cellular hydrophobic compartments. This suggests that the approach should be quantitative when testing compounds for this type of activity in vitro; effect/no effect is not the most pertinent question. The present study demonstrates how a set of reference compounds can be used in attempts to identify compounds that act by a more specific (chemical) mechanism to disturb the spindle function. All experiments were performed with an established cell line (V79 Chinese hamster). The results suggest that there is a good qualitative coupling in these cells between c-mitosis and aneuploidy with chemical treatment. Among compounds that are particularly active in relation to their lipophilic character are some chlorophenols, caffeine, diamide, diethyl maleate, 1-chloro-2,4-dinitrobenzene and tertiary butylhydroperoxide. This points to Ca2+-sequestering by mitochondria and/or cellular pH regulation (chlorophenols), Ca2+ release and sequestering by the endoplasmic reticulum (caffeine), enzymatic conjugation to glutathione (diethyl maleate, chlorodinitrobenzene) and hydroperoxide metabolism (t-butylhydroperoxide) as important target functions for specific activity.     

Inhibition of protein kinase CK2 by condensed polyphenolic derivatives. An in vitro and in vivo study

ATP site-directed inhibitors that can target individual kinases are powerful tools for use in signal transduction research, all the more so in the case of a pleiotropic, constitutively active protein kinase such as CK2, which is not turned on in response to specific stimuli. By screening a library of more than 200 derivatives of natural polyphenolic compounds, we have identified 16 molecules which inhibit CK2 with IC(50) values of 相似文献   

Possible coding for recognition of sexes,individuals and species in anal gland volatiles of Mustela eversmanni and M. sibirica

With a combination of solvent extraction and gas chromatography-mass spectrometry, we found eight new compounds in the two sympatric Mustela species, M. eversmanni and M. sibirica. These compounds had not been detected by headspace sampling with solvent desorption. Two of the newly detected compounds are nitrogen-containing compounds, indole and o-aminoacetophenone and the remaining are sulfur-containing volatiles. By comparing same and opposite sexes between the two Mustela species, we found that qualitative differences in the anal gland secretion are most likely to be used to code for information about species, corresponding to the idea of digital coding. In the Siberian weasel (M. sibirica), both presence or absence of sex-specific compounds (Z-2-ethyl-3-methylthietane only in females) and relative abundance of some compounds between males and females could be used to code for information about sex, corresponding to the idea of digital and analog coding, respectively. In the steppe polecat (M. eversmanni), only quantitative differences provided the possibility for inter-sexual communication. Thus coding for information about sex appeared to be digital. Coding for individual information could also be either digital or analog or both through the presence or absence of certain compounds and/or the difference in the relative abundances of certain compounds among individuals. Comparing with other Mustela spp., we failed to find a congruence between the chemical composition of anal gland secretions and the phylogenetic relationship among the species in this genus.     

Ligninase of Phanerochaete chrysosporium. Mechanism of its degradation of the non-phenolic arylglycerol beta-aryl ether substructure of lignin.

This study examined the ligninase-catalysed degradation of lignin model compounds representing the arylglycerol beta-aryl ether substructure, which is the dominant one in the lignin polymer. Three dimeric model compounds were used, all methoxylated in the 3- and 4-positions of the arylglycerol ring (ring A) and having various substituents in the beta-ether-linked aromatic ring (ring B), so that competing reactions involving both rings could be compared. Studies of the products formed and the time courses of their formation showed that these model compounds are oxidized by ligninase (+ H2O2 + O2) in both ring A and ring B. The major consequence with all three model compounds is oxidation of ring A, leading primarily to cleavage between C(alpha) and C(beta) (C(alpha) being proximal to ring A), and to a lesser extent to the oxidation of the C(alpha)-hydroxy group to a carbonyl group. Such C(alpha)-oxidation deactivates ring A, leaving only ring B for attack. Studies with C(alpha)-carbonyl model compounds corresponding to the three basic model compounds revealed that oxidation of ring B leads in part to dealkoxylations (i.e. to cleavage of the glycerol beta-aryl ether bond and to demethoxylations), but that these are minor reactions in the model compounds most closely related to lignin. Evidence is also given that another consequence of oxidation of ring B in the C(alpha)-carbonyl model compounds is formation of unstable cyclohexadienone ketals, which can decompose with elimination of the beta-ether-linked aromatic ring. The mechanisms proposed for the observed reactions involve initial formation of aryl cation radicals in either ring A or ring B. The cation radical intermediate from one of the C(alpha)-carbonyl model compounds was identified by e.s.r. spectroscopy. The mechanisms are based on earlier studies showing that ligninase acts by oxidizing appropriately substituted aromatic nuclei to aryl cation radicals [Kersten, Tien, Kalyanaraman & Kirk (1985) J. Biol. Chem. 260, 2609-2612; Hammel, Tien, Kalyanaraman & Kirk (1985) J. Biol. Chem. 260, 8348-8353].     

How marginal are phrasal compounds? Generalized insertion, expressivity, and I/Q-interaction

For several reasons, phrasal compounds like I-told-you-so attitude are a typical case of a marginal type of word-formation: (i) integration of a phrase into the word should not be allowed (violation of the No Phrase Constraint), (ii) lexical integrity is weakened (violation of the Principle of Lexical Integrity), (iii) they display an expressive flavour typical of marginal morphology. Using the mixed model of Ackema and Neeleman (2004) that allows for insertion from phrasal syntax into word syntax (Generalized Insertion) it is shown that phrasal compounds are by no means marginal from a purely theoretical point of view. However, the expressivity of marginal compounds has to be explained. Drawing on experimental data, it is shown that ad hoc phrasal compounds are understandable and witty to a high degree. These results are explained within the Presumptive Meanings approach of Levinson (2000) that develops the notion of Generalized Conversational Implicature (GCI). It is shown that the expressivity of ad hoc phrasal compounds stems from a word-level conflict between observing the I-principle (that favours the enrichment of underdetermined structures) on the one hand, and the Q-principle (that requires maximal information) on the other.     

Full replacement of the function of the secondary electron acceptor phylloquinone(= vitamin K1) by non-quinone carbonyl compounds in green plant photosystem I photosynthetic reaction centers

One-carbonyl quinonoid compounds, fluorenone (fluoren-9-one), anthrone, and their derivatives are introduced into spinach photosystem (PS) I reaction centers in place of the intrinsic secondary electron acceptor phylloquinone (= vitamin K1). Anthrone and 2-nitrofluorenone fully mediated the electron-transfer reaction between the reduced primary electron acceptor chlorophyll A0- and the tertiary electron acceptor iron-sulfur centers. It is concluded that the PS I phylloquinone-binding site has a structure that enables various compounds with different molecular structures to function as the secondary acceptor and that the reactions of incorporated compounds are mainly determined by their redox properties rather than by their molecular structure. Carbonyl groups increase the binding affinity of the quinone/quinonoid compounds but do not seem to be essential to their function. The quinonoid compounds as well as quinones incorporated into the PS I phylloquinone-binding sites are estimated to function at redox potentials more negative than in organic solvents.     

Comparison of the sensitivity of evaporative universal detectors and LC/MS in the HILIC and the reversed-phase HPLC modes

It was hypothesized that the hydrophilic interaction liquid interface chromatography (HILIC) mode should produce more response than the reversed-phase HPLC mode on detectors with an evaporative component to the detection process. HILIC mobile phases are mostly composed of polar organic solvent and are more volatile than reversed-phase mobile phases. Therefore the more easily evaporated HILIC mobile phases should produce greater sensitivity for those detectors that remove mobile phase by evaporation. The responses of 12 compounds were measured in the reversed-phase mode and the HILIC mode with three detectors: evaporative light scattering detector (ELSD), corona charged aerosol detector (cCAD), and electrospray mass spectrometry (ESI-MS). The compounds studied were very polar compounds that were retained in the HILIC mode. Generally, the HILIC mode was able to achieve greater sensitivity than the reversed-phase mode for these compounds. The increases in sensitivity observed can be attributed to the more volatile HILIC mobile phase. For the ELSD, the HILIC mode produced slightly greater sensitivity than the reversed-phase mode. The cCAD was approximately 10 times more sensitive in the HILIC mode and the ESI-MS was approximately 5–10 times more sensitive in the HILIC mode. There was one instance in the study where a compound produced more response in the reversed-phase mode. Thymine yielded more sensitivity in the reversed-phase mode with the ESI-MS detector. In a given mode of operation, there was significant variation in the measured response factors for all compounds on each detector. While this is not unexpected for the ESI-MS detector, variation in the response factors between compounds indicates that the cCAD and ELSD are not truly universal detectors in the sense that all compounds have identical responses.     

Platinum complexes with anticancer potential and their evaluation by a colorimetric lambda prophage induction assay

A simple biochemical phage induction assay (BIA) showed significant activity with 90% of the antitumor platinum compounds tested and lack of activity for all Pd(II) compounds and Pt(II) cationic complexes, compounds that are expected to be inactive. Structure-activity relationships for a large number of chemicals can be studied simultaneously by this simple, rapid, inexpensive and quantitative biochemical assay. Fifty-three platinum complexes were tested, including a number of ethylenediamines synthesized for this work. The magnitude of inducing activity varied over a 25-fold range; differences among analogs reflected structural differences in a chemically consistent manner. Seven platinum complexes showed greater activity than that of cis-diamminedichloroplatinum(II) (cisplatin, cis-DDP), while other compounds appeared to be substantially less toxic. The assay was predictive for most compounds with very high or very low activity in vivo against L1210. For compounds with intermediate levels of activity, no correlation between inducing and antitumor activity was observed.     

Structure-activity relationship of hydroxamate-based inhibitors on the secretases that cleave the amyloid precursor protein, angiotensin converting enzyme, CD23, and pro-tumor necrosis factor-alpha

Multiple proteins are proteolytically shed from the membrane, including the amyloid precursor protein (APP) involved in Alzheimer's disease, the blood pressure regulating angiotensin converting enzyme (ACE), the low affinity IgE receptor CD23, and the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). The inhibitory effect of a range of hydroxamic acid-based compounds on the secretases involved in cleaving and releasing these four proteins has been examined to build up a structure-activity relationship. Compounds have been identified that can discriminate between TNF-alpha convertase and the other three secretases (compound 15), between the shedding of CD23 and the shedding of APP and ACE (compound 21), and between the secretases and matrix metalloproteinase-1 (compound 22). The structure-activity relationship for the APP alpha-secretase and the ACE secretase were remarkably similar, and both secretases were activated in whole cell systems by the serine proteinase inhibitor 3,4-dichloroisocoumarin. The basal and carbachol-stimulated shedding of APP and ACE from human SH-SY5Y neuroblastoma cells could not be differentiated by any of the hydroxamate compounds, implying that the same or very similar activities are involved in the constitutive and regulated shedding of these two proteins. By utilizing a key discriminatory compound (compound 15) that potently inhibits TNF-alpha convertase but not alpha-secretase, we show that TNF-alpha convertase is not involved in the regulated shedding of APP from human neuronal cells. The compounds reported here will be useful in future studies aimed at identifying and validating candidate secretases.     

Structure-activity relationship study of flavone compounds with anti-HIV-1 integrase activity: a density functional theory study

Human immunodeficiency virus type-1 integrase (HIV-1 IN) is an essential enzyme for effective viral replication. Flavone compounds have been very much studied due to their activity during the inhibition process of HIV-1 IN. In this study, we employed density functional theory (DFT) using the B3LYP hybrid functional to calculate a set of molecular properties for 32 flavonoid compounds with anti-HIV-1 IN activity. The stepwise discriminant analysis (SDA), principal component analysis (PCA) and hierarchical cluster analysis (HCA) methods were employed to reduce dimensionality and investigate possible relationship between the calculated properties and the anti-HIV-1 IN activity. These analyses showed that the molecular hydrophobicity (ClogP), charge on atom 11 and electrophilic index (omega) are responsible for the separation between anti-HIV-1 IN active and inactive compounds.     

灯盏花挥发性组分结构与保留时间关系研究

通过对有机化合物非氢原子进行分类、参数化染色、建立非氢原子之间的关系得到新的结构描述符.对灯盏花的64种挥发性有机化合物结构进行了参数化表征,运用多元线性回归(MLR)和偏最小二乘回归(PLS)方法构建了化合物结构与色谱保留时间的关系模型.通过“留一法”交互检验对模型的稳定性进行了评价,利用外部样本集对模型的预测能力进...     

Synthesis,docking studies,in vitro cytotoxicity evaluation and DNA damage mechanism of new tyrosine-based tripeptides

Peptides are one of the leading groups of compounds that have been the subject of a great deal of biological research and still continue to attract researchers' attention. In this study, a series of tripeptides based on tyrosine amino acids were synthesized by the triazine method. The cytotoxicity properties of all compounds against human cancer cell lines (MCF-7), ovarian (A2780), prostate (PC-3), and colon cancer cell lines (Caco-2) were determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay method, and % cell viability and logIC50 values of the compounds were calculated. Significant decreases in cell viability were observed in all cells (p < 0.05). The comet assay method was used to understand that the compounds that showed a significant decrease in cell viability had this effect through DNA damage. Most of the compounds exhibited cytotoxicity by DNA damage mechanism. Besides, their interactions between investigated molecule groups with PDB ID: 3VHE, 3C0R, 2ZCL, and 2HQ6 target proteins corresponding to cancer cell lines, respectively, were investigated by docking studies. Finally, molecules with high biological activity against biological receptors were determined by ADME analysis.     

Theoretical studies on the structures and detonation properties of nitramine explosives containing benzene ring

The nitramine compounds containing benzene ring were optimized to obtain their molecular geometries and electronic structures at DFT-B3LYP/6-31+G(d) level. The theoretical molecular density (ρ), heat of formation (HOF), energy gap (ΔE(LUMO-HOMO)), charge on the nitro group (-Q(NO2)), detonation velocity (D) and detonation pressure (P), estimated using Kamlet-Jacobs equations, showed that the detonation properties of these compounds were excellent. It is found that there are good linear relationships between density, heat of formation, detonation velocity, detonation pressure and the number of nitro group. The simulation results reveal that molecule G performs similarly to famous explosive HMX, and molecule H outperforms HMX. According to the quantitative standard of energetics as an HEDC (high energy density compound), molecule H essentially satisfies this requirement. These results provide basic information for molecular design of novel high energetic density compounds.     

In silico search for multi-target anti-inflammatories in Chinese herbs and formulas

Chinese herbs were screened for compounds which may be active against four targets involved in inflammation, using pharmacophore-assisted docking. Multiple LigandScout (LS) pharmacophores built from ligand–receptor complexes in the protein databank (PDB) were first employed to select compounds. These compounds were then docked using LS-derived templates and ranked according to docking score. The targets comprised cyclo-oxygenases 1 & 2 (COX), p38 MAP kinase (p38), c-Jun terminal-NH₂ kinase (JNK) and type 4 cAMP-specific phosphodiesterase (PDE4). The results revealed that multi-target inhibitors are likely to be relatively common in Chinese herbs. Details of their distribution are given, in addition to experimental evidence supporting these results. Examples of compounds predicted to be active against at least three targets are presented, and their features outlined. The distribution of herbs containing predicted inhibitors was also analysed in relation to 192 Chinese formulas from over 50 herbal categories. Among those found to contain a high proportion of these herbs were formulas traditionally used to treat fever, headache, rheumatoid arthritis, inflammatory bowel disorders, skin disease, cancer, and traumatic injury. Relationships between multi-target drug discovery and Chinese medicine are discussed.     

Viscometric analysis of the interaction of bisphenanthridinium compounds with closed circular supercoiled and linear DNA.

The interaction with closed circular supercoiled and linear DNA of bisphenanthridinium compounds substituted through both the meta and para positions of the 6-phenyl group, along with appropriate monomer intercalators as controls, has been investigated by viscometric titration. When CPK models for the phenanthridinium rings of the three bis-compounds are oriented in a parallel manner as a model for intercalation, their ring plane to ring plane distances are approximately 7 to 8 A (SR 2430), 11 A (SR 2193), and 15 A (SR 2166). In SR 2430 the two phenanthridines are linked through the para positions of the 6-phenyl group; this chain allows intercalation of the two rings at adjacent binding sites in DNA, but is not long enough to accommodate an excluded site. The viscometric titrations with both superhelical and linear DNA clearly indicate that SR 2430 gives results close to those of the monomer control compounds while SR 2193 and SR 2166 have approximately twice the unwinding angle and DNA length increase on binding to DNA as the monomer compounds. These phenanthridinium compounds, therefore, are capable of bisintercalation only if their linking groups are of sufficient length to allow an excluded binding site between base pairs. This conclusion is supported by DNA thermal denaturation experiments in the presence of these compounds.     

Investigating the activity of 2-substituted alkyl-6-(2,5-dioxopyrrolidin-1-yl)hexanoates as skin penetration enhancers

Skin penetration enhancers are used in the formulation of transdermal delivery systems for drugs that are otherwise not sufficiently skin-permeable. We generated two series of esters by multi-step synthesis with substituted 6-aminohexanoic acid as potential transdermal penetration enhancers by multi-step synthesis. The synthesis of all newly prepared compounds is presented here. Structure confirmation of all generated compounds was accomplished by (1)H NMR, (13)C NMR, IR and MS spectroscopy. All the prepared compounds were analyzed using RP-HPLC and their lipophilicity (logk) was determined. The hydrophobicity (logP/ClogP) of the studied compounds was also calculated using two commercially available programs and 3D structures of the selected compounds were investigated by means of ab initio calculations of geometry and molecular dynamic simulations. All the synthesized esters were tested for their in vitro transdermal penetration-enhancing activity and showed higher enhancement ratios than oleic acid. The highest enhancement ratios were exhibited by compound 5f (C((2)) substituted with piperidine-2-one, C(11) ester chain) and 5a (C((2)) substituted with piperidine-2-one, C(6) ester chain). The series with a ω-lactam ring (piperidin-2-one; 5a-g), showed slightly higher activities than those with morpholine (6a-6g). All of the agents showed minimal anti-proliferative activity (IC(50) >6.25μM), indicating they would have low cytotoxicity when administered as chemical penetration enhancers. The relationships between the lipophilicity and the chemical structure of the studied compounds, as well as the correlation between their chemical structure and transdermal penetration-enhancing activity, are discussed.