7＇-O-菊酰基井冈羟胺A的合成

将拟除虫菊酸酰化后，与井冈霉素A的水解产物井冈羟胺A反应．合成了3个未见报道的7＇-O-菊酰基井冈羟胺A（4a～4c），其结构经^1H NMR、IR和MS确认。初步的生物活性测试显示，其中4a和4b均表现出一定的杀蚜虫活性，4b对纹枯病菌也表现出一定的抑制作用。     

井冈羟胺A的制备及纯化研究进展

井冈霉素(validam ycin)是目前防治水稻纹枯病最常用的最有效的农药之一,是我国自主研究开发的一种生物源农用抗生素,目前在我国使用量最大。井冈霉素A裂解生成井冈胺类物质,包括井冈羟胺A(validoxylam ine)、井冈霉胺(validam ine)、井冈霉烯胺(valienam ine)、井冈霉醇胺(valiolam ine)等主要产物,其中井冈羟胺A是井冈霉素主要的活性单元,其对离体海藻糖酶抑制活性要明显高于井冈霉素A,具有开发成为新型、高效、对人畜无害的农用抗生素的潜力。同时有研究表明井冈羟胺A可开发为糖苷酶抑制剂,对于井冈羟胺A的研究具有重要的意义,因此对井冈羟胺A的生物活性及其制备和纯化进行了论述。     

海藻糖酶抑制剂井冈羟胺A的制备与表征

在酸性介质中催化水解井冈霉素制备井冈羟胺A,收率69％。产物的化学结构经IR、MS、^1H NMR、^13C NMR和^1H-^1HCOSY确认,证实与日本武田公司的井冈羟胺A结构相同。     

多粘类芽孢杆菌和井冈霉素A配比对水稻纹枯病菌的室内毒力测定及田间药效

[目的]通过室内试验筛选出多粘类芽孢杆菌和井冈霉素A对水稻纹枯病具有增效作用的配比。[方法]室内试验和田间试验分别采用菌落生长抑制率测定法和常规喷雾法。[结果]多粘类芽孢杆菌与井冈霉素A以7∶3复配后增效最明显,田间药效试验中验证了该配比的防治效果。[结论]该混剂用药量与12.5%井冈·蜡芽菌AS相同时,防治效果优于12.5%井冈·蜡芽菌AS,与30%苯甲·丙环唑乳油(150 g a.i./hm2)防治效果相当。     

解淀粉芽胞杆菌JDF-6·井冈霉素A组合物对油茶炭疽病室内毒力测定及林间试验

[目的]筛选出解淀粉芽胞杆菌JDF-6与井冈霉素A防治油茶炭疽病的最佳配比。[方法]运用Horsfall法、孙云沛方法、林间防治试验测定解淀粉芽胞杆菌JDF-6和井冈霉素A对油茶炭疽病的增效作用。[结果]Horsfall法显示,解淀粉芽胞杆菌JDF-6和井冈霉素A在2颐8~8颐2(体积比)的范围内都有增效作用,1颐1时增效比最大,增效值C为1.50;孙云沛方法也显示解淀粉芽胞杆菌JDF-6与井冈霉素A 1颐1时增效系数CTC值达148.43,增效显著;以该比例为基础加工的30 g/L JDF-6·井冈霉素A水剂,当施药剂量高于675 g a.i./hm2时,对油茶炭疽病的防效为75%以上。[结论]解淀粉芽胞杆菌JDF-6和井冈霉素A混配比例为1颐1时是防治油茶炭疽病的良好配方。     

阿维菌素成分分析

利用液相色谱串联质谱技术分析了阿维菌素制剂的成分,使用反相柱,以甲醇-水为流动相,共分离出9个组分,并根据其质谱的加合离子和特征子离子,对其化学组成进行了推断.发现其中5个组分为已鉴定的阿维菌素成分A1a、A1b、A2a、B1a、B2a,另外4个组分为未被鉴定的阿维菌素成分.     

黄酮中间体乙酰酚酯化合物的合成与晶体结构

以4-羟基苯甲酸甲酯、4-羟基-3-甲氧基苯甲酸甲酯和4-羟基-3,5-二甲氧基苯甲酸甲酯为原料,分别与乙酸酐反应,合成了3个4-乙酰氧基苯甲酸甲酯类化合物,其结构通过元素分析和X-射线单晶衍射表征确征.4-乙酰氧基苯甲酸甲酯(2a)属单斜晶系,C2/c空间群,晶胞参数为a=25.400(4)(A)、b=5.9738(10)(A)、c=12.746(2)(A)、V=1928.5(6) (A)3.3-甲氧基-4-乙酰氧基苯甲酸甲酯(2b)属单斜晶系,P-1P212121空间群,晶胞参数为a=5.5523(7)(A)、b=12.7610(17)(A)、c=15.374(2)(A)、V=1089.3 (2)(A)3.3,5-二甲氧基-4-乙酰氧基苯甲酸甲酯((2)c)属单斜晶系,Pbca空间群,晶胞参数为a=18.0207(13)(A)、b=7.6885(5)(A)、c=18.2326(13)(A)、V=2526.2(3)(A)3.     

单晶体KTi0.93Sn0.07OPO4的结构研究

采用熔盐法自发成核生长出单晶体KTi0.93Sn0.07OPO4；使用X射线四圆衍射仪测定了该晶体的结构为：斜方晶系，空间群Pna21，晶胞常数a=12.831A,b=6.410A,c=10.584A。部分Sn^4 离子替代Ti^4 离子导致该晶体中氧八面体更趋对称性，进而改变了晶体的物理性质。     

HPO法制备己内酰胺的羟胺化过程研究

在70 kt/a磷酸羟胺(HPO)法制备己内酰胺工业装置上,对硝酸盐催化还原制备磷酸羟胺的反应影响因素进行探讨。结果表明:羟胺化过程反应温度控制58~62℃,反应压力为2 500~2 550 kPa,氢分压为38%~40%,催化剂浓度为6.5~9.6 kg/m3,气体循环量体积分数为46.0~48.0 km3/h,羟胺反应器出口pH值为1.80~2.00,控制羟胺反应进料组分中H+浓度为2.90~3.10 mol/kg、H2PO4-浓度2.30~2.45mol/kg、NH4+浓度为2.50~3.00 mol/kg时,羟胺钯/碳(Pd/C)催化剂的活性和选择性能达到最佳值,磷酸羟胺的收率达0.98~1.03 mol/kg。     

酪氨酸激酶抑制剂的合成及抗肿瘤活性

以4-氯-6,7-二甲氧基喹唑啉、8-溴辛酸乙酯及溴代正丁烷等为原料,根据喹唑啉类化合物药效结构关系,对N-(3-氯-4-烷氧苯基)喹唑啉-4-胺类化合物(ARRY-334543)进行了结构修饰,合成了具有抗肿瘤细胞活性的酪氨酸激酶抑制剂(Ⅷa~c、Ⅸa和Ⅸb)。采用NMR和MS对抑制剂的结构进行了表征,并对其进行了抗肿瘤细胞活性测试。得到的化合物Ⅸa和Ⅸb均对MCF-7、BGC-823、A549、DU145和H1975细胞有一定的抗肿瘤活性,其中,活性最好的是化合物Ⅸa,其对MCF-7细胞的半数抑制浓度(GI50)为0.37μmol/L。     

Synthesis and Evaluation of Novel Oxyalkylated Derivatives of 2′,4′-Dihydroxychalcone as Anti-Oomycete Agents against Bronopol Resistant Strains of Saprolegnia sp.

A series of novel oxyalkylchalcones substituted with alkyl groups were designed and synthesized, and the antioomycete activity of the series was evaluated in vitro against Saprolegnia strains. All tested O-alkylchalcones were synthesized by means of nucleophilic substitution from the natural compound 2′,4′-dihydroxychalcone (1) and the respective alkyl bromide. The natural chalcone (1) and 10 synthetic oxyalkylchalcones (2–11) were tested against Saprolegnia parasitica and Saprolegnia australis. Among synthetic analogs, 2-hydroxy,4-farnesyloxychalcone (11) showed the most potent activity against Saprolegnia sp., with MIC and MOC values of 125 µg/mL (similar to bronopol at 150 µg/mL) and 175 µg/mL, respectively; however, 2′,4′-dihydroxychalcone (1) was the strongest and most active molecule, with MIC and MOC values of 6.25 µg/mL and 12.5 µg/mL.     

Spectrofluorimetric and Computational Investigation of New Phthalimide Derivatives towards Human Neutrophil Elastase Inhibition and Antiproliferative Activity

Herein, nine phthalimide-based thiazoles (4a–4i) were synthesized and investigated as new human neutrophil elastase (HNE) inhibitors using spectrofluorimetric and computational methods. The most active compounds containing 4-trifluoromethyl (4c), 4-naphthyl (4e) and 2,4,6-trichloro (4h) substituents in the phenyl ring exhibited high HNE inhibitory activity with IC₅₀ values of 12.98–16.62 µM. Additionally, compound 4c exhibited mixed mechanism of action. Computational investigation provided a consistent picture of the ligand-receptor pattern of inter-actions, common for the whole considered group of compounds. Moreover, compounds 4b, 4c, 4d and 4f showed high antiproliferative activity against human cancer cells lines MV4-11, and A549 with IC₅₀ values of 8.21 to 25.57 µM. Additionally, compound 4g showed high activity against MDA-MB-231 and UMUC-3 with IC₅₀ values of 9.66 and 19.81 µM, respectively. Spectrophotometric analysis showed that the most active compound 4c demonstrated high stability under physiological conditions.     

Novel N-Substituted 3-Aryl-4-(diethoxyphosphoryl)azetidin-2-ones as Antibiotic Enhancers and Antiviral Agents in Search for a Successful Treatment of Complex Infections

A novel series of N-substituted cis- and trans-3-aryl-4-(diethoxyphosphoryl)azetidin-2-ones were synthesized by the Kinugasa reaction of N-methyl- or N-benzyl-(diethyoxyphosphoryl)nitrone and selected aryl alkynes. Stereochemistry of diastereoisomeric adducts was established based on vicinal H3–H4 coupling constants in azetidin-2-one ring. All the obtained azetidin-2-ones were evaluated for the antiviral activity against a broad range of DNA and RNA viruses. Azetidin-2-one trans-11f showed moderate inhibitory activity against human coronavirus (229E) with EC₅₀ = 45 µM. The other isomer cis-11f was active against influenza A virus H1N1 subtype (EC₅₀ = 12 µM by visual CPE score; EC₅₀ = 8.3 µM by TMS score; MCC > 100 µM, CC₅₀ = 39.9 µM). Several azetidin-2-ones 10 and 11 were tested for their cytostatic activity toward nine cancerous cell lines and several of them appeared slightly active for Capan-1, Hap1 and HCT-116 cells values of IC₅₀ in the range 14.5–97.9 µM. Compound trans-11f was identified as adjuvant of oxacillin with significant ability to enhance the efficacy of this antibiotic toward the highly resistant S. aureus strain HEMSA 5. Docking and molecular dynamics simulations showed that enantiomer (3R,4S)-11f can be responsible for the promising activity due to the potency in displacing oxacillin at β-lactamase, thus protecting the antibiotic from undesirable biotransformation.     

N-苄基吲哚类熊果酸衍生物的合成及抗肝癌活性

为开发高效低毒的抗肝癌天然产物衍生物,依据药物拼合原理设计并合成了一系列未见文献报道的熊果酸衍生物.将熊果酸与不同取代的N-苄基吲哚片段通过Claisen-Schmidt缩合反应得到目标化合物,其化学结构均经过核磁氢谱、核磁碳谱以及质谱的联合确证.采用噻唑蓝(MTT)法考察其体外抗肝癌活性,结果表明,2-{[1-(2-...     

Design,Synthesis, Molecular Docking Analysis and Biological Evaluations of 4-[(Quinolin-4-yl)amino]benzamide Derivatives as Novel Anti-Influenza Virus Agents

In this study, a series of 4-[(quinolin-4-yl)amino]benzamide derivatives as the novel anti-influenza agents were designed and synthesized. Cytotoxicity assay, cytopathic effect assay and plaque inhibition assay were performed to evaluate the anti-influenza virus A/WSN/33 (H1N1) activity of the target compounds. The target compound G07 demonstrated significant anti-influenza virus A/WSN/33 (H1N1) activity both in cytopathic effect assay (EC₅₀ = 11.38 ± 1.89 µM) and plaque inhibition assay (IC₅₀ = 0.23 ± 0.15 µM). G07 also exhibited significant anti-influenza virus activities against other three different influenza virus strains A/PR/8 (H1N1), A/HK/68 (H3N2) and influenza B virus. According to the result of ribonucleoprotein reconstitution assay, G07 could interact well with ribonucleoprotein with an inhibition rate of 80.65% at 100 µM. Furthermore, G07 exhibited significant activity target PA−PB1 subunit of RNA polymerase according to the PA−PB1 inhibitory activity prediction by the best pharmacophore Hypo1. In addition, G07 was well drug-likeness based on the results of Lipinski’s rule and ADMET prediction. All the results proved that 4-[(quinolin-4-yl)amino]benzamide derivatives could generate potential candidates in discovery of anti-influenza virus agents.     

Ginsenoside Re Protects against Serotonergic Behaviors Evoked by 2,5-Dimethoxy-4-iodo-amphetamine in Mice via Inhibition of PKCδ-Mediated Mitochondrial Dysfunction

It has been recognized that serotonin 2A receptor (5-HT_2A) agonist 2,5-dimethoxy-4-iodo-amphetamine (DOI) impairs serotonergic homeostasis. However, the mechanism of DOI-induced serotonergic behaviors remains to be explored. Moreover, little is known about therapeutic interventions against serotonin syndrome, although evidence suggests that ginseng might possess modulating effects on the serotonin system. As ginsenoside Re (GRe) is well-known as a novel antioxidant in the nervous system, we investigated whether GRe modulates 5-HT_2A receptor agonist DOI-induced serotonin impairments. We proposed that protein kinase Cδ (PKCδ) mediates serotonergic impairments. Treatment with GRe or 5-HT_2A receptor antagonist MDL11939 significantly attenuated DOI-induced serotonergic behaviors (i.e., overall serotonergic syndrome behaviors, head twitch response, hyperthermia) by inhibiting mitochondrial translocation of PKCδ, reducing mitochondrial glutathione peroxidase activity, mitochondrial dysfunction, and mitochondrial oxidative stress in wild-type mice. These attenuations were in line with those observed upon PKCδ inhibition (i.e., pharmacologic inhibitor rottlerin or PKCδ knockout mice). Furthermore, GRe was not further implicated in attenuation mediated by PKCδ knockout in mice. Our results suggest that PKCδ is a therapeutic target for GRe against serotonergic behaviors induced by DOI.     

Novel 1,3,5-Triazinyl Aminobenzenesulfonamides Incorporating Aminoalcohol,Aminochalcone and Aminostilbene Structural Motifs as Potent Anti-VRE Agents,and Carbonic Anhydrases I,II, VII,IX, and XII Inhibitors

A series of 1,3,5-triazinyl aminobenzenesulfonamides substituted by aminoalcohol, aminostilbene, and aminochalcone structural motifs was synthesized as potential human carbonic anhydrase (hCA) inhibitors. The compounds were evaluated on their inhibition of tumor-associated hCA IX and hCA XII, hCA VII isoenzyme present in the brain, and physiologically important hCA I and hCA II. While the test compounds had only a negligible effect on physiologically important isoenzymes, many of the studied compounds significantly affected the hCA IX isoenzyme. Several compounds showed activity against hCA XII; (E)-4-{2-[(4-[(2,3-dihydroxypropyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (31) and (E)-4-{2-[(4-[(4-hydroxyphenyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (32) were the most effective inhibitors with K_Is = 4.4 and 5.9 nM, respectively. In addition, the compounds were tested against vancomycin-resistant Enterococcus faecalis (VRE) isolates. (E)-4-[2-({4-[(4-cinnamoylphenyl)amino]-6-[(4-hydroxyphenyl)amino]-1,3,5-triazin-2-yl}amino)ethyl]benzenesulfonamide (21) (MIC = 26.33 µM) and derivative 32 (MIC range 13.80–55.20 µM) demonstrated the highest activity against all tested strains. The most active compounds were evaluated for their cytotoxicity against the Human Colorectal Tumor Cell Line (HCT116 p53 +/+). Only 4,4’-[(6-chloro-1,3,5-triazin-2,4-diyl)bis(iminomethylene)]dibenzenesulfonamide (7) and compound 32 demonstrated an IC₅₀ of ca. 6.5 μM; otherwise, the other selected derivatives did not show toxicity at concentrations up to 50 µM. The molecular modeling and docking of active compounds into various hCA isoenzymes, including bacterial carbonic anhydrase, specifically α-CA present in VRE, was performed to try to outline a possible mechanism of selective anti-VRE activity.     

两种含二茂铁基schiff 碱的合成及其抑菌活性

通过乙酰基二茂铁与两种杂环胺(4-氨基安替比林,2-氨基-5-巯基-1,3,4-噻二唑)缩合合成了两种含二茂铁基的Schiff碱(a、b),产率分别为85.8%和72.6%,并通过IR、1HNMR及元素分析对其结构进行了确证。最后,将合成出的两种Schiff碱分别对3种细菌(金黄色葡萄球菌、大肠杆菌、枯草芽孢杆菌)进行了初步抑菌实验,将其结果与非杂环类Schiff碱Fc-C(CH3)NC6H5=(c)的抑菌性能做了比较。结果表明,Schiff碱对上述3种细菌都有抑制作用,且抑菌效果随着Schiff碱浓度的增大而增强。此外,杂环类Schiff碱(a、b)对上述3种细菌的抑菌活性明显优于非杂环类Schiff碱(c)。     

A Galantamine–Curcumin Hybrid Decreases the Cytotoxicity of Amyloid-Beta Peptide on SH-SY5Y Cells

Misfolded amyloid beta (Aβ) peptides aggregate and form neurotoxic oligomers. Membrane and mitochondrial damages, calcium dysregulation, oxidative stress, and fibril deposits are among the possible mechanisms of Aβ cytotoxicity. Galantamine (GAL) prevents apoptosis induced by Aβ mainly through the ability to stimulate allosterically the α7 nAChRs and to regulate the calcium cytosolic concentration. Here, we examined the cytoprotective effects of two GAL derivatives, namely compounds 4b and 8, against Aβ cytotoxicity on the human neuroblastoma cell line SH-SY5Y. The protective effects were tested at simultaneous administration, pre-incubation and post-incubation, with Aβ. GAL and curcumin (CU) were used in the study as reference compounds. It was found that 4b protects cells in a similar mode as GAL, while compound 8 and CU potentiate the toxic effects of Aβ. Allosteric stimulation of α7 nAChRs is suggested as a possible mechanism of the cytoprotectivity of 4b. These and previous findings characterize 4b as a prospective non-toxic multi-target agent against neurodegenerative disorders with inhibitory activity on acetylcholinesterase, antioxidant, and cytoprotective properties.     

3,5-二取代-1,2,4-(噁)二唑类衍生物的合成及生物活性

[目的]为了寻找具有良好生物活性的噁二唑类衍生物。[方法]以苯甲腈为原料,经加成、脱水环化等反应设计合成了一系列未见文献报道的噁二唑类衍生物,并对目标化合物进行了生物活性测试。[结果]其结构通过1H NMR、13C NMR和H RMS图谱得以确证。初步生物活性测试结果显示:部分目标化合物在质量浓度200 mg/L下对南方根结线虫有较好的抑制活性,其中化合物5f、6a、6b和6e对线虫的抑制率达到90%以上,尤其化合物4a、4d对线虫的抑制率达到100%,另外部分目标化合物对南方根结线虫和小菜蛾幼虫都具有一定的抑制活性。[结论]该类结构具有较好的生物活性,有进一步优化的潜力。