含4(3H)-喹唑啉酮结构的取代1,3,4-噁二唑(噻二唑)化合物的合成及抗菌活性研究

以2-胺基苯甲酸为原料,通过环化、缩合、肼解、环化、硫醚化和氧化等步骤,合成了10个含喹唑啉酮取代1,3,4-噁二唑(噻二唑)化合物。通过1H NMR、13C NMR、MS 和元素分析进行确证其结构。初步抑菌活性测试表明,化合物浓度在50 μg/mL时,对葡萄座腔菌(Botryosphaeria dothidea)、拟茎点霉菌(Phomopsis sp.)和灰霉菌(B. cinerea)具有中等抑制活性。另外,目标化合物对猕猴桃溃疡病(Pseudomonas syringae pv. actinidia)均具有一定的抑制活性,其中化合物6a和6b对猕猴桃溃疡病的EC50值为11.7 μg/mL和20.5 μg/mL,优于对照药剂叶枯唑(24.5 μg/mL)。这类化合物具有较好抗菌的生物活性,在此基础上进行结构优化,有望发现较高活性化合物。     

5-亚环己基-2-取代氨基咪唑啉酮类化合物的合成及其杀菌活性研究

以环己酮和2-硫代乙内酰脲为起始原料,经Knoevenagel缩合反应制得5-亚环己基-2-硫代咪唑啉-4-酮(1),化合物1在乙醇钠/乙醇体系中与碘甲烷反应得到5-亚环己基-2-甲硫基咪唑啉-4-酮(2),化合物2再与相应的取代苯胺或苄胺在冰醋酸体系中回流制得目标化合物5-亚环己基-2-取代氨基咪唑啉酮3a～3r,它们的化学结构经1H NMR,IR,MS和X-ray单晶衍射确证.5-亚环己基-2-对氯苄氨基咪唑啉酮(3q):Mr=335.83,C16H18ClN3O CH4O,Monoclinic,P2(1)/n,ρ=1.264 g/cm3,F(000)=712,Z=4,a=0.59895(12)nm,b=1.2161(2)nm,c=2.4289(5)nm,β=94.03(3)°.初步生物活性测定结果表明:在50μg/mL浓度下,部分目标化合物均对供试菌种显现出一定的抑制活性,其中5-亚环己基-2-对氟苄氨基咪唑啉酮(3p)对油菜菌核的EC50为24.37μg/mL,3q对辣椒疫霉的EC50为28.68μg/mL.     

含吖啶基的单环β-内酰胺及噻唑啉酮衍生物的合成及其生物活性

9-吖啶基甲醛芳亚胺席夫碱分别与氯乙酰氯、苄氧乙酰氯在三乙胺作用下产生的烯酮发生[2+2]环加成反应和巯基乙酸的合环反应,合成了9个1-芳基-3-取代-4-(9-吖啶基)-氮杂环丁-2-酮衍生物L1~L6和2-(9-吖啶基)-3-芳基-1,3-噻唑烷-4-酮衍生物T1~T3,对所合成的化合物进行了体外抗癌活性和白细胞共同抗原活性筛选.结构表明,当样品浓度为10μmol/L时,化合物L4对肿瘤细胞HL-60(Leucocythemia人白血病细胞)生长的抑制率为79.4%.当样品浓度为20μg/mL时,化合物L5,L6和T3对细胞分裂周期磷酸酯酶Cdc25B(Cell division cycle 25B phosphatase)的抑制率分别为80.64%,99.75%和99.34%.当样品浓度为20μmol/mL时,化合物L6和T3对CD45(leukocyte common antigen,LCA白细胞共同抗原)蛋白酪氨酸磷酸酶A的抑制率分别为86.12%和91.03%.在此基础上,初步讨论了该类化合物的构效关系.     

含磺酰胺结构的1,3,4-噁二唑砜类化合物的设计、合成及抗菌活性研究

为了寻找新型抗菌剂,采用活性亚结构拼接,设计合成了23个含磺酰胺结构的1,3,4-噁二唑砜类化合物,并对其抗菌活性进行了测试.在100μg/m L浓度下,大多数化合物对水稻细菌性条斑病菌(Xanthomonas oryzae pv.oryzicola)和水稻白叶枯病菌(Xanthomonas oryzae pv.oryzae)表现出优异的离体抗菌活性.除N-((5-(丙基磺酰基)-1,3,4-噁二唑-2-基)甲基)-4-(三氟甲基)苯磺酰胺(18)外,所有化合物对水稻细菌性条斑病菌的半数有效浓度(EC₅₀)值为1.3～22.5μg/mL所有化合物对水稻白叶枯病菌的EC₅₀为1.1～32.7μg/m L,均优于对照药剂叶枯唑(84.1和71.4μg/mL)和噻菌酮(122.1和84.0μg/m L).此外,4-氟-N-((5-(甲基磺酰基)-1,3,4-噁二唑-2-基)甲基)苯磺酰胺(4)可以通过抑制胞外多糖(EPS)的产生、生物膜的形成以及改变细胞膜的通透性和细胞表面形态,从而抑制水稻细菌性条斑病菌和水稻白叶枯病菌的正常生长.     

含咪唑啉2,4-二酮的新型磷酰胺酯类化合物的合成和生物活性

在合成含咪唑啉2,4-二酮磷酸酯和磷酰胺类化合物的基础上,根据Hydantocidin在植物体内的作用形式是Hydantocidin 5’-phosphate的特点,将5-[4-羟基-3-硝基-苯(苄)基]-2,4-咪唑啉二酮中间体与O,N-二烷基硫代磷酰氯反应合成得到了18个结构新颖的O-烷基-N-烷基-5-[4-羟基-3-硝基-苯(苄)基]-2,4-咪唑啉二酮硫代磷酰胺酯类化合物,其结构通过IR,1H NMR,31P NMR和元素分析表征.初步生物测定结果表明,化合物O-乙基(丙基)-N-异丙基-5-(4-羟基-3-硝基苄基)-2,4-咪唑啉二酮硫代磷酰胺酯(B10,B16)在100μg/mL浓度下对油菜的抑制率为64.1%和69.6%,O-甲基-N-正丁基-5-(4-羟基-3-硝基苄基)-2,4-咪唑啉二酮硫代磷酰胺酯(B15)对蚜虫和小菜蛾均表现了良好的杀虫活性,在300μg/mL浓度下24 h的校正死亡率分别为100%和95%.     

新型含2,4-咪唑啉二酮的4-甲基-3-苯基-2-酰亚胺噻唑啉的合成及生物活性

通过酰氯制备异硫氰酸酯,与5-(4-氨基苄基)-2,4-咪唑啉二酮反应合成了含2,4-咪唑啉二酮的N-苯甲酰基-N'-苯基硫脲,然后在三乙胺存在下再与溴丙酮发生碱催化缩合反应以中等以上收率合成了新型含2,4-咪唑啉二酮的4-甲基-3-苯基-2-酰亚胺噻唑啉,它们的化学结构经1H NMR,IR,HR-ESI-MS和化合物3g和4g的X-ray单晶衍射表征,硫脲与溴丙酮的反应机理通过化合物3g和4g的晶体结构得到进一步确证.初步生物活性测定结果表明:部分目标化合物对供试昆虫及菌种显现出良好的抑制活性,如在200 mg/L浓度下化合物3i和4q对小菜蛾的死亡率分别为86%和100%,在50 mg/L浓度下化合物4n对油菜菌核菌的抑制率为82.6%,而它们对油菜和稗草显示出微弱但并不特征的除草活性.     

5-(4-羟基苯基)-2,4-咪唑啉二酮酯类化合物的合成及其生物活性

在模拟AdSS酶天然抑制剂结构合成5-(4-羟基苄基)-2,4-咪唑啉二酮酯系列化合物的基础上,为优化其结构,以5-(4-羟基苯基)-2,4-咪唑啉二酮为中间体,合成了28个未见文献报道的5-(4-羟基苯基)-2,4-咪唑啉二酮羧酸酯类化合物,它们的结构均经IR,1HNMR和元素分析表征.初步生物活性测试表明目标化合物5-(4-羟基苯基)-2,4-咪唑啉二酮对叔丁基苯甲酸酯(2i)和2-噻吩酸酯(3b)在浓度200μg/mL时对拟南芥生长抑制率达70%..     

含2,4-咪唑啉二酮的环十二酮衍生物的合成及杀菌活性

以环十二酮为原料合成α-取代环十二酮和α-取代环十二二酮,再与2,4-咪唑啉二酮膦酸酯和2-硫代-2,4-咪唑啉二酮分别发生Wittig-Horner反应和Knoevenagel缩合反应,合成了一系列目标化合物,它们的化学结构通过IR,1HNMR,13C NMR和元素分析进行了表征.初步生物活性测试结果表明,部分化合物10,11A,11B,12A,12B,13A,14B和16在50μg/mL浓度时对芦笋茎枯、茄绵疫以及油菜菌核病菌均有优良的抑制活性,抑制率在70%～98%之间,进一步的生物测试结果表明,化合物12B,13A和14B对芦笋茎枯的EC50值分别为15.80,31.34和44.26 μg/mL.     

含喹唑啉酮的查尔酮衍生物的设计、合成及生物活性研究

设计合成了25个含喹唑啉酮的查尔酮衍生物.抗病毒生物实验结果表明,(E)-3-(4-氯苯基)-6-氟-2-((2-(4-(3-(4-甲氧基苯基)丙烯酰基)苯氧基)乙基)硫代)喹唑啉-4(3H)-酮(Z12)对烟草花叶病毒(tobacco mosaic virus, TMV)有较好的抑制活性,治疗和保护的EC50值分别为94.3和98.8μg/mL,优于对照药宁南霉素(ningnanmycin,NNM)的216.1和189.6μg/mL.透射电镜结果表明,Z12使得TMV病毒颗粒断裂,形成长短不一的棒状结构,微量热涌动实验(MST)的结果表明, Z12对烟草花叶病毒外壳蛋白(TMV-CP)结合的Kd值为(0.033±0.014)μmol/L,优于宁南霉素的Kd值[(0.106±0.024)μmol/L],说明了Z12对TMV-CP具有更强的结合力.抑菌实验结果表明,部分化合物对水稻白叶枯病菌(Xanthomonas oryzae pv. Oryzae, Xoo)和柑桔溃疡病菌(Xanthomonas axonopodis pv. Citri, Xac)表现出优异活性,其中(E)-2-((...     

5-[4-羟(氨)基苄基]-2-硫代-2,4-咪唑啉二酮磺酸酯(酰胺)的合成及其生物活性

以5-(4-羟基/氨基苄基)-2-硫代-2,4-咪唑啉二酮为原料,在三乙胺作傅酸剂的条件下与取代磺酰氯反应,得到28个新的5-(4-羟基/氨基苄基)-2-硫代-2,4-咪唑啉二酮苯磺酸酯/酰胺类化合物,它们的化学结构经1H NMR,MS和元素分析确证.初步生测结果表明:在100μg/mL浓度下,部分目标化合物均对供试植物病原菌和油菜显现出一定的抑制活性,如5-(4-氨基苄基)-2-硫代-2,4-咪唑啉二酮对碘苯磺酰胺(4d)对黄瓜灰霉病菌抑制率为80.7%,5-(4-羟基苄基)-2-硫代-2,4-咪唑啉二酮邻甲基苯磺酸酯(3n)和5-(4-氨基苄基)-2-硫代-2,4-咪唑啉二酮-2,4-二氯苯磺酰胺(4m)对油菜的生长抑制率分别为87.4%和81.5%.     

Phenolic glucosides and chromane analogs from the insect fungus Conoideocrella krungchingensis BCC53666

Six new compounds, named conoideoglucosides A − C and conoideochromanes A − C, together with eight known compounds, including eutypinic acid, 2,2-dimethyl-2H-1-chromene-6-carboxylic acid, (−)-luteoskyrin, (−)-4a-oxyluteoskyrin, chrysophanol, islandicin, catenarin, and (22E)-5α,8α-epidioxyergosta-6,22-dien-3β-ol were isolated from the insect fungus Conoideocrella krungchingensis BCC53666. (−)-Luteoskyrin exhibited a broad range of antimicrobial activity such as antimalarial (IC₅₀ 0.51 μg/mL), antitubercular (MIC 6.25 μg/mL), antibacterial (both Gram positive; MIC 0.39–1.56 μg/mL and Gram negative; MIC 3.13–12.50 μg/mL), and antifungal (against various plant pathogens; MIC 3.13–50.00 μg/mL) activities, while (−)-4a-oxyluteoskyrin and catenarin showed weaker antibacterial activity. Moreover, eutypinic acid, (−)-luteoskyrin, (−)-4a-oxyluteoskyrin, and catenarin showed cytotoxicity against NCI-H187 cells with IC₅₀ in a range of 0.16–17.99 μg/mL, while eutypinic acid and catenarin had no cytotoxicity against non-cancerous (Vero) cells at maximum tested concentration (50 μg/mL). The complete NMR spectral data and biological activity of the known (−)-4a-oxyluteoskyrin was also reported for the first time.     

含6-氟喹唑啉片段的新型1,3,4-噁(噻)二唑类衍生物的合成及抗菌活性研究

为寻找高效农用抗菌先导化合物,通过活性亚结构拼接法设计合成了50个含6-氟喹唑啉片段的新型1,3,4-噁(噻)二唑类衍生物6 a?6 y和8a?8y,其结构经¹H NMR、¹³C NMR和HRMS手段进行了表征,且化合物6i和8x的结构最终由X射线单晶衍射法加以确认.初步抗菌测试表明,部分化合物表现出较好的体外抗真菌活性.在50μg/m L浓度下,化合物6b、6d、6t、6v和6x对小麦赤霉病菌的抑制率分别为58%、58%、55%、63%和60%,化合物6 v和8v对苹果腐烂病菌的抑制率分别为71%和64%,化合物6 v对油菜炭疽病菌的抑制率为72%,它们均优于对照药剂噁霉灵(分别为51%、61%和70%).此外,部分化合物在100μg/m L浓度下也表现出一定的体外抗细菌活性.     

Synthesis,Characterization and Antibacterial Activity of New 5-Aryl Pyrazole Oxime Ester Derivatives

Eleven new 1-{5-[4-（benzyloxy）phenyl]-3-methyl-4,5-dihydropyrazol-l-yl} oxime ester dcrivatives were synthesized and characterized by elemental analysis, HRMS, ^1H NMR data. All the compounds were screened for their antibacterial potential in vitro against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. The results indicate that compounds 8c and 8f possess potent activity with the minimum inhibitory concentrations（MIC） of 1.562--3.125 ug/mL against all the four bacteria. Compounds 8c, 8e and 8f show moderate inhibition against the DNA gyrase（IC50=1.9--2.5 ug/mL）. On the basis of the biological activities, structure-activity relationship was discussed.     

Design,Synthesis, and in vitro Antimicrobial Activity of New Furan/Thiophene‐1,3‐Benzothiazin‐4‐one Hybrids

This study presents the design, synthesis, spectral analysis, and in vitro antimicrobial evaluation of a new series of furan/thiophene‐1,3‐benzothiazin‐4‐one hybrids ( 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ). New compounds were obtained by cyclization reaction of N‐substituted furan/thiophene‐2‐carboxamide derivatives ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ) with thiosalicylic acid. All synthesized compounds were screened for their in vitro antimicrobial activities using the broth microdilution method. Nine of the synthesized compounds showed good activity against Gram‐positive, Gram‐negative bacteria, and yeasts belonging to Candida spp. (MIC = 7.81–500 μg/mL), especially against Staphylococcus spp. (MIC = 15.62–62.5 μg/ml), Bacillus spp. (MIC = 7.81–62.5 μg/mL), Bordetella bronchiseptica ATCC 4617 (MIC = 62.5–125 μg/mL), and fungistatic activity against Candida spp. (MIC = 62.5–125 μg/mL).     

Synthesis and antifungal activity of novel sulfone derivatives containing 1,3,4-oxadiazole moieties

A series of new sulfone compounds containing 1,3,4-oxadiazole moieties were synthesized. The structures of these compounds were confirmed by spectroscopic data (IR, 1H- and 13C-NMR) and elemental analyses. Antifungal tests indicated that all the title compounds exhibited good antifungal activities against eight kinds of plant pathogenic fungi, and some showed superiority over the commercial fungicide hymexazol. Among them, compounds 5d, 5e, 5f, and 5i showed prominent activity against B. cinerea, with determined EC?? values of 5.21 μg/mL, 8.25 μg/mL, 8.03 μg/mL, and 21.00 μg/mL, respectively. The present work demonstrates that sulfone derivatives such as 5d containing a 1,3,4-oxadiazole moiety can be used as possible lead compounds for the development of potential agrochemicals.     

Nematocidal flavone-C-glycosides against the root-knot nematode (Meloidogyne incognita) from Arisaema erubescens tubers

A screening of several Chinese medicinal herbs for nematicidal properties showed that Arisaema erubescens (Wall.) Schott tubers possessed significant nematicidal activity against the root-knot nematode (Meloidogyne incognita). From the ethanol extract, two nematicidal flavone-C-glycosides were isolated by bioassay-guided fractionation. The compounds were identified as schaftoside and isoschaftoside on the basis of their phytochemical and spectral data. Schaftoside and isoschaftoside possessed strong nematicidal activity against M. incognita (LC(50) = 114.66 μg/mL and 323.09 μg/mL, respectively) while the crude extract of A. erubescens exhibited nematicidal activity against the root-knot nematode with a LC(50) value of 258.11 μg/mL.     

Synthesis, characterization, and antimicrobial evaluation of oxadiazole congeners

A series of 1,3-oxazole, 1,3-thiazole, isomeric 1,2,4-oxadiazole, 1,3,4-oxadiazole, and 1,2,3,4-tetrazole heterocycles was synthesized. All the compounds shared as a common feature the presence of a 4-hydroxyphenyl substituent. The structures of the synthesized compounds were confirmed by MS, 1H-NMR, and elemental analysis. In vitro antimicrobial activity for all the newly synthesized compounds at concentrations of 200-25 μg/mL was evaluated against Gram+ve organisms such as methicillin-resistant Staphylococcus aureus (MRSA), Gram-ve organisms such as Escherichia coli (E. coli), and the fungal strain Aspergillus niger (A. niger) by the cup plate method. Ofloxacin and ketoconazole (10 μg/mL) were used as reference standards for antibacterial and antifungal activity, respectively. Compounds 15, 16, and 20 showed notable antibacterial and antifungal activities at higher concentrations (200 μg/mL), whereas 17-19 were found to display significant antibacterial or antifungal activity (25-50 μg/mL) against the Gram+ve, Gram-ve bacteria, or fungal cells used in the present study.     

Indeno[1,2-b]pyridin-5-one derivatives containing azo groups and their hydrazonal precursors: Synthesis,antimicrobial profile,DNA gyrase binding affinity,and molecular docking

The prevalence of germs that are resistant to many antibiotics is rising rapidly the world over. There is a large group of researchers actively looking for better medicines. Here, we designed two series of hydrazonal and indeno[1,2-b]pyridin-5-one bearing hydrazone and azo-groups to test their antimicrobial activity. Molecular structures of all derivatives were assured based on their spectral data and elemental analyses. Results of the antimicrobial activity of the tested hydrazone and azo compounds showed promising potential for several derivatives. The minimum inhibitory concentrations (MICs) of hydrazones 4a - h and 6a - g displayed good antibacterial reactivities with a range of 3.91–250 μg/mL and moderate antifungal activity with a range of 15.6–500 μg/mL. The most promising hydrazone 4f and azo- 6a compounds demonstrated MIC values against Streptococcus faecalis and Escherichia coli equal to 3.91 and 7.81 μg/mL, respectively. Moreover, azo compound 6a showed MIC value equal to 3.91 μg/mL against Enterobacter cloacae species. Additionally, derivative 4f exhibited a significant inhibitory profile against the E. coli gyrase A enzyme (IC₅₀ = 5.53 μg/mL). On the other hand, compound 6a (IC₅₀ 14.05 μg/mL) exhibited the lowest DNA gyrase inhibitory activity as compared to compounds 4f and reference standard drug novobiocin, IC₅₀ 5.53 and 1.88 μg/mL, respectively. Pharmacokinetic and pharmacodynamic profiles and molecular docking studies for the two most promising molecules 4f and 6a were computed and revealed that both compounds have good ADME profiles and high binding affinity to DNA gyrase binding site.     

Antibacterial, antifungal and cytotoxic activities of two flavonoids from Retama raetam flowers

We have investigated the antibacterial, antifungal and cytotoxic activities of two flavonoids isolated from Retama raetam flowers using the disc diffusion and micro-dilution broth methods. The cytotoxic activity was tested against Hep-2 cells using the MTT assay. The compounds licoflavone C (1) and derrone (2) were active against Pseudomonas aeruginosa and Escherichia coli (7.81-15.62 μg/mL) and showed important antifungal activity. Strong antifungal activity against Candida species (7.81 μg/mL) was for example found with compound 2. The tested compounds also showed strong cytotoxicity against Hep-2 cells. These two compounds may be interesting antimicrobial agents to be used against infectious diseases caused by many pathogens.