Synthesis,Antibacterial and Anthelmintic Activity of Novel 3-(3-Pyridyl)-oxazolidinone-5-methyl Ester Derivatives

In this study, a series of 3-(3-pyridyl)-oxazolidone-5-methyl ester derivatives was synthesized and characterized by ¹H NMR, ¹³C NMR, and LC-MS. The conducted screening antibacterial studies of the new 3-(3-pyridyl)-oxazolidone-5-methyl ester derivatives established that the methyl sulfonic acid esters have broad activity spectrum towards Staphylococcus aureus, Streptococcus pneumoniae, Bacillus subtilis and Staphylococcus epidermidis. Among them, compound 12e has the most potent activity, with an MIC of 16 μg/mL against B.subtilis, and could reduce the instantaneous growth rate of bacteria. Furthermore, molecular docking studies were also simulated for compound 12e to predict the specific binding mode of this compound. In addition, anthelmintic activity of these compounds was also evaluated against adult Indian earthworms (Pheretima posthuman). The results showed that compound 11b had the best effect. These results above can provide experimental reference for the development of novel antibacterial and anthelmintic drugs.     

Evaluation of Anthelmintic and Anti-Inflammatory Activity of 1,2,4-Triazole Derivatives

Parasitic diseases, caused by intestinal helminths, remain a very serious problem in both human and veterinary medicine. While searching for new nematicides we examined a series of 1,2,4-triazole derivatives 9–22, obtained during reactions of N³-substituted amidrazones with itaconic anhydride. Two groups of compounds, 9–16 and 17–22, differed in the position of the double bond on the methacrylic acid moiety. The toxicity of derivatives 9–22 and the anti-inflammatory activity of 12 and 19–22 were studied on peripheral blood mononuclear cells (PBMC). Antiproliferative activity of compounds 12 and 19–22 was tested cytometrically in PBMC cultures stimulated by phytohemagglutinin. The influence of derivatives 12 and 19–22 on the TNF-α, IL-6, IL-10 and IFN-γ production was determined by ELISA in lipopolysaccharide-stimulated PBMC cultures. Anthelmintic activity of compounds 10–22 was studied in the Rhabditis sp. nematodes model. Most compounds (11–22) proved to be non-toxic to human PBMC. Derivatives 19–22 showed anti-inflammatory activity by inhibiting the proliferation of lymphocytes. Moreover, compounds 12 and 19–22 significantly reduced the production of TNF-α and derivatives 19–21 decreased the level of INF-γ. The strongest anti-inflammatory activity was observed for compound 21. Compounds 12 and 14 demonstrated anthelmintic activity higher than albendazole and may become promising candidates for anthelmintic drugs.     

Isolation and identification of two new compounds from the Penicillium sp. SYPF7381

Abstract

Two new compounds, (7R, 2E, 5E)-3,5,7-trimethyl-2,5-octadienedioic-8-methyl ester (1) and neovasipyridone G (3), together with a new natural product compound (7R,2E,5E)-3,5,7-trimethyl-2,5-octadienedioic acid (2), and six known compounds (4–9) were isolated from Penicillium sp. SYPF7381. Their structures were elucidated on the basis of extensive spectroscopic analysis, and the absolute configurations of compounds 1 and 2 were determined by optical rotation. The absolute configuration of compound 3 was determined by means of electronic circular dichroism (ECD) calculation. In addition, the in vitro anti-inflammatory activities of all compounds were assayed in RAW 264.7 cells by assessing LPS-induced NO production. Furthermore, the structure-antiinflammation activity relationships for these isolated compounds were summarized based on the experimental as well as the docking results.     

Synthesis,Crystal Structure and Biological Activity of a New 4,5-Diaryl-1H-imidazole Derivative

A new 4,5-diaryl-1H-imidazole was synthesized and characterized by 1H NMR, ESI-MS, elemental analysis and FT-IR. The crystal structure of the title compound(C19H16Cl2N2O2, Mr = 375.24) has been determined by single-crystal X-ray diffraction. Crystal parameters: monoclinic system, space group P21/n, a = 14.349(3), b = 8.7918(18), c = 15.352(3) , β = 108.56(3)°, V = 1836.1(6) 3, Z = 4, F(000) = 776, Dc = 1.357 g/cm3, μ = 0.368 mm-1, the final R = 0.0502 and wR = 0.1066 for 2324 observed reflections with I 2σ(I). A total of 16117 reflections were collected, of which 3615 were independent(Rint = 0.0595). The preliminary bioassay suggested that the title compound exhibits distinct effective inhibition on the proliferation of cancer cell lines.     

3,5-Dibromo-2-methoxybenzoic acid from sea spongeDidiscus sp.

3,5-Dibromo-2-methoxybenzoic acid was isolated from sea spongeDidiscus sp. The structure of the title compound was established by spectral methods, by X-ray diffraction analysis, and by comparing with a synthetic sample prepared from salicylaldehyde. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2363–2365, November, 1998.     

Crystal Structure and Activity against Acetaminophen-induced Hepatotoxicity of a Potassium Complex with Taurine-5-bromosalicylaldehyde Schiff Bases

A novel potassium complex KC9H9NO4SBr has been synthesized and characterized by IR spectra and single-crystal X-ray diffraction method. The crystal belongs to orthorhombic, space group Pbca with a = 0.74040（15）, b = 0.74960（15）, c = 4.2620（9） nm, V = 2.3654（8） nm^3, Mr = 346.24, Dc = 1.945 g/cm^3, Z = 8, F（000） = 1376, μ（MoKa） = 4.005mm^-1, GOOF = 1.021, R = 0.0471 and wR = 0.0872. In the crystal, the potassium ion is typically eight-coordinated, surrounded by eight O atoms from six （E）-2-（5-bromo-2-hydroxy-benzyli-deneamino）ethanesulfonate anions. The neighboring potassium ions are bridged by sulfonate groups into a two-dimensional layer structure, above and below which the 5-bromo-2-hydroxy-benzene rings are protruded. The activity against acetaminophen-induced hepatotoxicity of this complex was also studied, and found it can protect liver from hepatotoxicity induced by acetaminophen （AAP） to some extent.     

Discovery of New Ginsenol-Like Compounds with High Antiviral Activity

A number of framework amides with a ginsenol backbone have been synthesized using the Ritter reaction. We named the acetamide as Ginsamide. A method was developed for the synthesis of the corresponding amine and thioacetamide. The new compounds revealed a high activity against H1N1 influenza, which was confirmed using an animal model. Biological experiments were performed to determine the mechanism of action of the new agents, a ginsamide-resistant strain of influenza virus was obtained, and the pathogenicity of the resistant strain and the control strain was studied. It was shown that the emergence of resistance to Ginsamide was accompanied by a reduction in the pathogenicity of the influenza virus.     

N-[2-(4-甲基)嘧啶基]-N′-2-硝基苯磺酰脲的合成、晶体结构、生物活性及其与酵母AHAS的分子对接

合成了磺酰脲化合物N-[2-(4-甲基)嘧啶基]-N′-2-硝基苯磺酰脲, 用元素分析、红外、核磁共振氢谱对产物进行了表征, 培养并测定了其晶体结构. 晶体属三斜晶系, 空间群, 晶胞参数a＝0.54159(1) nm, b＝1.1533(3) nm, c＝1.1857(4) nm, α＝83.907(6)°, β＝81.048(5)°, γ＝77.637(4)°, V＝0.7126(4) nm³, D_c＝1.572 g/cm³, Z＝2, F(000)＝348, R＝0.0659, wR＝0.1217. 在晶体结构中, 杂环上的一个N原子与脲桥上邻近的N原子上的H构成分子内氢键. 测定了对酵母AHAS的离体抑制活性, 其抑制常数K_i为(2.48±0.35)×10^－7 mol/L. 用分子对接方法, 将目标化合物晶体结构对接到靶酶酵母AHAS的活性位点, 发现对接完毕目标化合物的构象与复合物晶体中的磺酰脲分子构象接近, 并得到了合理的生物活性预测值. 该研究为进一步理解磺酰脲类的分子结构、药物活性并设计新的分子提供了帮助和指导.     

The structure of a new copper(II) complex with 3-methyl-5-carboxylatopyrazole

Molecular and crystal structures of a new complex compound of copper(II) with 3-methyl-5-carboxylatopyrazole (CH₃PzCOO^?) with the composition Cu(CH₃PzCOO)₂·H₂O have been determined by single crystal XRD. It has been demonstrated that the carboxylate ion performs the bridging tridentate function. In the equatorial plane coordination occurs through the pyridine N atom of the pyrazole and one of O atoms of the carboxylate group yielding a five-membered metallocycle CuNOC₂. The second O atom of one of the ligands is bound to the neighboring copper(II) ion affording an infinite linear chain. The coordination polyhedron of the copper atom is a square pyramid, coordination core CuN₂O₃.     

Dihydroisocoumarin derivatives with antifouling activities from a gorgonian-derived Eurotium sp. fungus

Five pairs of new dihydroisocoumarin enantiomers, (±)-eurotiumides A–E, and two related racemates, (±)-eurotiumides F and G, were isolated from a gorgonian-derived fungus, Eurotium sp. XS-200900E6. The enantiomeric separations for (±)-eurotiumides A–E were achieved by chiral-HPLC, and their absolute configurations were determined by ECD spectra. All of the isolated compounds are rare dihydroisocoumarin derivatives with a methoxy at C-4. (+)- And (−)-eurotiumides B and D with cis configurations of H-3/H-4 exhibited potent antifouling activities against the larval settlement of the barnacle Balanus amphitrite with the EC₅₀ values ranging from 0.7 to 2.3 μg/mL, and displayed high therapeutic ratios (LC₅₀/EC₅₀ >15). The tested compounds also showed extensive antibacterial activities. It was the first report of antifouling activities for dihydroisocoumarin derivatives.     

Discovery of Cysteine and Its Derivatives as Novel Antiviral and Antifungal Agents

Based on the structure of the natural product cysteine, a series of thiazolidine-4-carboxylic acids were designed and synthesized. All target compounds bearing thiazolidine-4-carboxylic acid were characterized by ¹H-NMR, ¹³C-NMR, and HRMS techniques. The antiviral and antifungal activities of cysteine and its derivatives were evaluated in vitro and in vivo. The results of anti-TMV activity revealed that all compounds exhibited moderate to excellent activities against tobacco mosaic virus (TMV) at the concentration of 500 μg/mL. The compounds cysteine (1), 3–4, 7, 10, 13, 20, 23, and 24 displayed higher anti-TMV activities than the commercial plant virucide ribavirin (inhibitory rate: 40, 40, and 38% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively), especially compound 3 (inhibitory rate: 51%, 47%, and 49% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively) with excellent antiviral activity emerged as a new antiviral candidate. Antiviral mechanism research by TEM exhibited that compound 3 could inhibit virus assembly by aggregated the 20S protein disk. Molecular docking results revealed that compound 3 with higher antiviral activities than that of compound 24 did show stronger interaction with TMV CP. Further fungicidal activity tests against 14 kinds of phytopathogenic fungi revealed that these cysteine derivatives displayed broad-spectrum fungicidal activities. Compound 16 exhibited higher antifungal activities against Cercospora arachidicola Hori and Alternaria solani than commercial fungicides carbendazim and chlorothalonil, which emerged as a new candidate for fungicidal research.     

Structural and Physical Properties of New Conducting Cation Radical Salts with Te-Based Counteranions, Tetraiodotellurate(II) and Hexaiododitellurate(II)

This article reports preparation, structure, and conducting property of several cation radical salts of organic donors tetramethyltetrathiafulvalene (TMTTF), ethylenedithiotetrathiafulvalene (EDT-TTF), bis(ethylenedithio)tetrathiafulvalene (ET), bis(ethylenedithio)tetraselenafulvalene (BETS) and hexamethylenetetraselenafulvalene (HMTSF) with two novel planar Te-based dianions, TeI₄²⁻ and Te₂I₆²⁻. (ET)₅Te₂I₆ 1 and (BETS)₅Te₂I₆ 2 are isostructural. In these Te₂I₆²⁻ salts, intermolecular short I···I contacts form a supramolecular corrugated anion sheet. Donor arrangement is similar to the θ-type. With lowering temperature, the resistivity of 1 shows a gradual increase followed by a sharp upturn at 110 K. 2 is metallic down to 120 K and shows a gradual increase of the resistivity followed by a clear transition to an insulating state around 60 K. Crystal structure of (ET)₄TeI₄ 3 is based on the “herring bone” arrangement of ET molecules similar to the α-type. 3 shows a semiconductive behavior around room temperature followed by a transition to an insulating state at 210 K. (EDT-TTF)₄TeI₄ 4, a semiconductor, exhibits a unique two-dimensional arrangement of dimerized EDT-TTF molecules.     

Cytotoxic Activity and Docking Studies of 2-arenoxybenzaldehyde N-acyl Hydrazone and 1,3,4-Oxadiazole Derivatives against Various Cancer Cell Lines

To understand whether previously synthesized novel hydrazone and oxadiazole derivatives have promising anticancer effects, docking studies and in vitro toxicity assays were performed on A-549, MDA-MB-231, and PC-3 cell lines. The antiproliferative properties of the compounds were investigated using molecular docking experiments. Each compound’s best-docked poses, binding affinity, and receptor-ligand interaction were evaluated. Compounds’ molecular weights, logPs, TPSAs, abilities to pass the blood-brain barrier, GI absorption qualities, and CYPP450 inhibition have been given. When the activities of these molecules were examined in vitro, for the A-549 cell line, hydrazone 1e had the minimum IC₅₀ value of 13.39 μM. For the MDA-MB-231 cell line, oxadiazole 2l demonstrated the lowest IC₅₀ value, with 22.73 μM. For PC-3, hydrazone 1d showed the lowest C50 value of 9.38 μM. The three most promising compounds were determined as compounds 1e, 1d, and 2a based on their minimum IC₅₀ values, and an additional scratch assay was performed for A-549 and MDA-MB-231 cells, which have high migration capacity, for the three most potent molecules; it was determined that these molecules did not show a significant antimetastatic effect.     

Synthesis,Crystal Structure and Cytotoxic Activity of a New N-Vinyl-1H-dibenzo[a,c]carbazole Derivative of the Dehydroabietic Acid

The title compound （C29H33NO2, 3） was synthesized and structurally characterized by elemental analysis, IR, MS, 1H- and 13C-NMR and single-crystal X-ray diffraction. The crystal is of monoclinic system, space group P21 with a = 14.428（3）, b = 7.3440（15）, c = 22.768（5） A, β = 95.17（3）°, V = 2402.7（8） A3, Z = 4, Mr = 427.56, Dc = 1.182 g/cm3, F （000） = 920, 2（MoKa） = 0.71073 A,μ = 0.073 mm-1, the final R= 0.0670 and wR= 0.1002 for 2437 reflections with I〉 2σ（I） Two crystallographically independent molecules with different conformations co-exist in the structure. The crystal structure is stabilized by intermolecular C-H…π interactions which make the molecules stack along the b axis. In addition, the preliminary cytotoxic assay showed that the title compound exhibited moderate inhibitory activity against KB and SW1116 cells.     

Synthesis,Crystal Structure and Antitumor Activity of Mixed Ligand Coordination Compound of Copper with Norfloxacin and 1,10-Phen,[Cu(NFLX)(phen)(H_2O)] NO_3·3H_2O

Fluoroquinolones are the widely used antibiotics for treating of numerous diseases1-4. Norfloxacin(1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-1,4dihydroquinoline-3-carboxylicacid, NFLX) is a typical member of this family and its metal coordination compounds have also received much more attention5-11. Apart from the synthesis and physicochemical properties of the coordination compounds, their antibacterial properties were also tested7-13, but there was scare report on antitumor properties of th…     

5-嘧啶基-1,2,4-噁二唑衍生物的合成及生物活性研究

通过嘧啶甲酰氯与取代的苄胺肟反应得到一系列结构新颖的5-嘧啶基-1,2,4-噁二唑类化合物,并对其结构进行了表征,培养并测定了化合物5a的晶体结构;将目标化合物晶体结构对接到靶酶酵母乙酰辅酶A羧化酶(ACCase)的活性位点,发现目标化合物与复合物晶体中的禾草灵分子的构象及结合模式相似;初步生物活性测试表明部分化合物具有较好的除草活性.     

Antifungal Activity of Chemical Constituents from Piper pesaresanum C. DC. and Derivatives against Phytopathogen Fungi of Cocoa

In this study, the antifungal potential of chemical constituents from Piper pesaresanum and some synthesized derivatives was determined against three phytopathogenic fungi associated with the cocoa crop. The methodology included the phytochemical study on the aerial part of P. pesaresanum, the synthesis of some derivatives and the evaluation of the antifungal activity against the fungi Moniliophthora roreri, Fusarium solani and Phytophthora sp. The chemical study allowed the isolation of three benzoic acid derivatives (1–3), one dihydrochalcone (4) and a mixture of sterols (5–7). Seven derivatives (8–14) were synthesized from the main constituents, of which compounds 9, 10, 12 and 14 are reported for the first time. Benzoic acid derivatives showed strong antifungal activity against M. roreri, of which 11 (3.0 ± 0.8 µM) was the most active compound with an IC₅₀ lower compared with positive control Mancozeb^® (4.9 ± 0.4 µM). Dihydrochalcones and acid derivatives were active against F. solani and Phytophthora sp., of which 3 (32.5 ± 3.3 µM) and 4 (26.7 ± 5.3 µM) were the most active compounds, respectively. The preliminary structure–activity relationship allowed us to establish that prenylated chains and the carboxyl group are important in the antifungal activity of benzoic acid derivatives. Likewise, a positive influence of the carbonyl group on the antifungal activity for dihydrochalcones was deduced.