3-芳基-5-噻吩基二氢吡唑磺酰胺衍生物的合成及其抗炎活性研究

二氢吡唑是一类含有多种生物活性的五元氮杂环化合物,广泛存在于各种活性天然产物结构中。本文由4-氟苯乙酮和N-甲基哌嗪经取代反应后,再与2-噻吩甲醛发生羟醛缩合生成哌嗪取代噻吩查尔酮(2)。化合物2与水合肼环化得到中间体化合物3,最后经磺酰氯衍生化,合成得到8个未见报道的3-芳基-5-噻吩基二氢吡唑磺胺衍生物(4a～4h),其结构均经IR、~1H NMR和~(13)C NMR确证。采用小鼠巨噬细胞Raw264. 7模型初步测试了衍生物的抗炎活性,结果表明,化合物4a、4e和4h具有潜在的体外抗炎活性,特别是化合物4a抑制NO生成的IC_(50)值为12. 64μmol/L,与阳性对照药地塞米松活性相当。     

Synthesis and investigation of anti-inflammatory and anticonvulsant activities of novel coumarin-diacylated hydrazide derivatives

A number of novel coumarin derivatives synthesized by the reaction of 3-carbonyl chloride coumarin with some substituted aryl acid hydrazides to investigate their anti-inflammatory and anticonvulsant activities. Carrageenan (0.1 ml of 1%, w/v) was injected subplantarly in the right paw of rats to induce an acute model of inflammation. Anti-inflammatory efficacy was evaluated for 5 hours at 3 different dosages 5, 10, 25 mg/kg. After that, the changes in the level of paw edema volumes and percentage inhibition of all groups were observed and the most effective coumarin derivative was found as N'-(2-hyroxybenzoyl)-2-oxo-2H-chromene-3-carbohydrazide. In addition, N’-(2-oxo-2H-chromene-3-carbonyl)nicotinohydrazide, (E)-N’-(3-(4-hydroxyphenyl)acryloyl)-2-oxo-2H-chromene-3-carbohydrazide, and N’-(5-amino-2-hydroxybenzoyl)-2-oxo-2H-chromone-3-carbohydrazide showed their anti-inflammatory effects in a dose-dependent manner. On the other hand, pentylenetetrazole (PTZ, 80 mg/kg, i.p.)-induced seizure model was used to investigate the anticonvulsant activities of six newly synthesized coumarin derivatives in mice. Hybrid compound of salicylic acid hydrazide and 3-carbonyl chloride coumarin (8d) was found the most promising anticonvulsant agent among all treatment groups according to the onset of seizure and survival rate. Moreover, (E)-N'-cinnamoyl-2-oxo-2H-chromene-3-carbohyrazide (8b) and (E)-N'-(3-(4-hyroxyphenyl)acryloyl)-2-oxo-2H-chromene-3-carbohydrazide (8c) has potential anticonvulsant efficiency in low doses (30 mg/kg). The anticonvulsant effect of these coumarin derivatives may be through enhanced GABA-mediated inhibition in the brain.     

8-氨甲基取代木犀草素衍生物的合成和抗炎活性研究

以木犀草素为先导化合物,对其A环8-位碳上进行Mannich反应,合成了10个未见文献报道的8-氨甲基化衍生物,并用1HNMR,IR和MS(HRMS)进行了结构表征。利用二甲苯诱发小鼠耳廓肿胀模型对所合成的七个目标化合物进行了抗炎活性的药理筛选,初步结果表明部分化合物具有良好的抗炎活性。     

去氢木香内酯衍生物的合成及其抗炎活性研究

去氢木香内酯是一种含有多种生物活性的倍半萜化合物,广泛存在于药材云木香中。去氢木香内酯与伯胺化合物经Michael加成反应,合成得到5个新的去氢木香内酯衍生物(1～5),其结构均经¹H NMR、¹³C NMR和LC-MS确证。采用小鼠巨噬细胞Raw264.7模型初步测试了衍生物的抗炎活性和毒性,结果表明,化合物1对NO的生成抑制率为88±1.02%,表现出较好的抗炎活性,且在MTT实验中其对巨噬细胞的抑制率仅为3.75%,几乎无细胞毒性,可作进一步研究。     

Synthesis,characterization and evaluation of novel benzothiazole clubbed chromene derivatives for their anti-inflammatory potential

Abstract

A series of chromene derivatives (5a–f) were prepared by multistep synthesis process using 2-[3-phenyl prop-2-ene nitrile] 1,3-benzothiazole and dimedone using piperidine as catalyst in ethanol. The reaction was found to proceed via Knoevenagel condensation of aldehydes with benzothiazole, followed by the elimination to afford the 2-(benzo[d]thiazol-2-yl)-3-(aryl)acrylonitrile, which then undergoes Michael addition with 5,5-dimethyl-1,3-cyclohexanedione, followed by intramolecular O-cyclization to give the products. The structures of all novel constructed derivatives were corroborated by elemental analysis and spectral data (FT-IR, ¹H-NMR, ¹³C-NMR and Mass). Subsequently, the compounds were tested for their in-vivo anti-inflammatory activity. This study revealed that these synthesized derivatives tend to have significantly anti inflammatory activity and shall prove as structural templates in the design and development of new anti inflammatory drugs.     

含酰基哌嗪片段的呋喃查尔酮衍生物的合成及其抗炎活性研究

依据活性结构单元的拼合原理,以2-呋喃甲醛和4-氟苯乙酮为原料出发,经Aldol缩合、脱水、哌嗪取代反应生成4’-(1-哌嗪基)呋喃查尔酮(2)后,再与酰氯和磺酰氯反应,得到了10个未见报道的含哌嗪取代的呋喃查尔酮衍生物,其结构经~1H NMR和~(13)C NMR确证。采用小鼠巨噬细胞Raw 264.7模型初步测试了目标化合物的体外抗炎活性,结果表明,磺酰胺类化合物的抗炎活性要优于酰胺类化合物,特别是化合物4d能有效抑制NO的生成(IC_(50)=3.88μmol/L),与阳性对照药地塞米松活性相当。     

Synthesis and biological evaluation of andrographolide derivatives as potent anti-HIV agents

A series of Andro derivatives were described and evaluated for their anti-HIV activity in vitro.Compound 10 and 16b,of which TI were>10,had some anti-HTV-l activity in vitro.Therein,compound 10 which was the best potent compound,could serve as a new lead for further development of anti-AIDS agents.     

Antibacterial activity of methylated chitosan and chitooligomer derivatives: Synthesis and structure activity relationships

The purpose of this study was to synthesize series of methylated chitosaccharide derivatives, possessing various degree of methylation, and to determine their structure activity relationship (SAR) with regard to their antibacterial effect against Staphylococcus aureus. Chitosan polymer and chitooligomers were used as starting materials and were methylated by reaction with methyl iodide. Depending on the reaction conditions the degree of N-quaternization ranged from 0% to 74%, with varying degree of N,N-dimethylation, N-monomethylation and O-methylation. More selective N-quaternization could be obtained with protection group strategy. At pH 5.5 the chitosaccharide polymers and their methylated derivatives were active against S. aureus with minimal inhibitory concentration (MIC) ranging from 16 to 512 μg/mL. At pH 7.2 the non-quaternized derivatives were inactive but their highly N-quaternized derivatives showed MIC as low as 8 μg/mL. The chitooligomers, as well as their derivatives, were inactive at both pH’s. The SAR studies revealed that N-quaternization was mainly responsible for the antibacterial effects at pH 7.2, whereas it did not contribute to the antibacterial activity under acidic conditions.     

Synthesis and antifungal activity of trichodermin derivatives

<正>A series of derivatives were synthesized from trichodermin(1) which was an antifungal metabolite produced by Trichoderma taxi sp.nov.Their structures were confirmed by ~1H NMR,MS spectrum.Their antifungal activities were evaluated in vitro.The preliminary structure activity relationships(SAR) results indicated that the double bond,epoxide moiety and ester group were main pharmacophore elements,the stereochemistry of C4 position played a key role as well,and the compounds 1e-1g displayed stronger antifungal activity against Magnaporthe grisea than 1.     

二苯乙烯衍生物的合成及抗肿瘤活性

以甲氧基取代的4’-氨基二苯乙烯与4-溴甲基-5-甲基-1,3-二氧杂环戊烯-2-酮为原料,通过亲核取代反应合成得到了4种新的二苯乙烯衍生物。这些化合物的结构经NMR、IR和元素分析确定。以HeLa、SMMC-7721、BGC-823和A549为受试细胞株,用MTT法测试了这4种化合物的抗肿瘤活性。测试结果表明,这些化合物具有一定的抗肿瘤活性。     

3-芳基-5-(2-呋喃基)-4, 5-二氢吡唑衍生物的合成及其生物活性评价

二氢吡唑类化合物是一类具有良好生物活性的五元杂环化合物。本文以2-呋喃甲醛和4-氟苯乙酮为原料,经羟醛缩合和取代反应生成4’-二甲氨基呋喃查尔酮(2)后,与水合肼环化得到二氢吡唑中间体(3),再酰化得到9个未见报道的5-(2-呋喃基)-3-芳基-4, 5-二氢-1H-吡唑衍生物(4a-4i),其结构经IR、₁H NMR和₁₃C NMR确证。分别采用小鼠巨噬细胞Raw264.7模型和DHHP法初步测试了目标化合物的体外抗炎活性和抗氧化活性,结果表明,部分化合物具有潜在的抗炎活性和清除自由基活性,特别是化合物4b和4c的抗炎活性与阳性对照药地塞米松活性相当(IC₅₀值分别为7.84μM和10.52μM),而化合物3、4b、4c和4d在浓度为4mg/mL时对DPPH自由基的清除率均超过90%。     

An ancient remedial repurposing: synthesis of new pinocembrin fatty acid acyl derivatives as potential antimicrobial/anti-inflammatory agents

Five new pinocembrin derivatives (MC1-MC5) were synthesized by Steglich reaction, and investigated for their antimicrobial, antioxidant, and anti-inflammatory activity. MC2 (oleoyl derivative) and MC3 (linoleoyl derivative) have shown the highest inhibitory effects on bacterial proliferation, with MIC values of 32 μg/mL against Staphylococcus aureus. The docosahexaenoyl derivative MC5 displayed the highest anti-inflammatory activity, decreasing NO production in LPS-stimulated macrophages with an IC₅₀ value of 15.51 μg/mL higher than the positive control diclofenac (IC₅₀ of 39.71 μg/mL). All new synthesized compounds showed no anti-proliferative effects on RAW 264.7 cells. Results demonstrated as the introduction of fatty acid substituents improved the biological profile of pinocembrin. Moreover, the chemical nature of substituents significantly affects the bioactivity. These preliminary results outline the importance to investigate the synthesis of pinocembrin fatty acids derivatives as new and safe anti-microbial/anti-inflammatory agents.     

Quantitative structure activity relationships of 5-nitrofuran derivatives

Summary Quantitative structure-activity relationships were performed on a set of 5-nitrofuran derivatives. The correlation parameters used were hydrophobicity and connectivity. The former was measured by means of the capacity factor (log k _o ) obtained by HPLC and the latter through the molecular valence connectivity index^{1 v} obtained by computational methods. The biological activity data considered were growth inhibition percentages ofT. cruzi (GI % (48 h)) and half-maximal inhibitory concentration of Glutathione Reductase (I_{0.5 (max)}). Good adjustment, r=0.98, was obtained if a logarithmic model is used for I_{0.5 (max)} correlations. When GI% is considered, correlations were poorer and the consideration of both structural parameters was necessary for their improvement, r=0.94.     

苯二氮杂卓类化合物的合成及抗血吸虫活性研究

化合物B30属于苯二氮杂卓类化合物.体外实验表明,在50μM具有100％的杀灭血吸虫效果.本文利用药物化学生物电子等排等原理,设计、合成了4个B30衍生物6、10、13、16,并对其抗血吸虫活性进行初步体外评价.结果显示4个化合物均具有一定的杀虫能力.尤其化合物16有较好的抗血吸虫活性,在50μM浓度下血吸虫的存活率降...     

Synthesis and antifungal activity of chalcone derivatives

In the present study, using chalcone as a lead compound, a series of its derivatives (compounds 1–30) were designed and synthesised. Their activity of anti-pathogenic fungi of plants has been evaluated. It is found that these compounds have good antifungal activity against Sclerotinia sclerotiorum, Helminthosprium maydis, Botrytis cinerea, Rhizoctonia solani and Gibberella zeae. Among them, the inhibition of growth for compound 30 against S. sclerotiorum showed 89.9%, with the median effective concentrations (EC₅₀) of 15.4 μg mL^? 1. The inhibition of growth for compounds 28, 29 and 30 at a concentration of 100 μg mL^? 1 against H. maydis is 90.3%, 90.7% and 91.1%, with EC₅₀ of 15.1, 18.3 and 18.1μg mL^? 1, respectively.     

氮杂岩白菜素衍生物的合成及其初步抗肿瘤活性

岩白菜素因其广泛的生理活性而备受关注。本文通过Mannich和Mitsunobu反应,合成了8个氮杂岩白菜素衍生物,其结构经1H NMR、13C NMR及质谱确证。采用MTT法初步测试了目标化合物体外抗肿瘤活性,结果表明,化合物3c和3d对细胞株A549均表现出优于岩白菜素的抑制活性(IC50分别为3.74μmol/L和5.05μmol/L),可做进一步研究。     

Synthesis and anti-inflammatory activity of ethynylthiazoles

A series of acetylene derivatives of thiazole using the Sonogashira cross-coupling method was synthesized and evaluated in vivo for their anti-inflammatory activity. Four compounds exhibited good anti-inflammatory activity and two inhibited soybean lipoxygenase. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 769–774, May, 2006.     

新型香豆素类白藜芦醇衍生物的合成及其生物活性研究

白藜芦醇是一种具有广泛生物活性的茋类化合物。为了寻找活性较强的新型分子,以白藜芦醇为原料出发,经Vilsmeier甲酰化和Knoevenagel缩合,合成了3个未见文献报道的香豆素类白藜芦醇衍生物 (E)-7-羟基-5-(4-羟基苯乙烯基)香豆素（3a-3c）,其结构经1H NMR、13C NMR和HRMS确证。抗炎和抗氧化活性结果发现,化合物3a具有与地塞米松相当的抗炎活性,并对超氧阴离子和羟基自由基有较强的清除作用,可做进一步研究。     

3,5-二甲氧基苯乙烯环酮类化合物的合成及表征

研发环氧合酶(COSX)/5-脂氧酶(5-LOX)双重抑制剂是降低非甾体抗炎药胃肠道(GI)副作用的有效途径之一[1]。大多数二叔丁基苯酚类化合物具有较强的COX/5-LOX双重抑制作用,例如达布飞龙甲磺酸盐(darbufelone mesilate)用于治疗类风湿性关节炎和骨关节炎,GI不良反应小且长效,目前处     

Synthesis and antifungal activity evaluation of new heterocycle containing amide derivatives

A series of heterocycle containing amide derivatives (1–28) were synthesised by the combination of acyl chlorides (1a, 2a) and heterocyclic/homocyclic ring containing amines, and their in vitro antifungal activity was evaluated against five plant pathogenic fungi, namely Gibberella zeae, Helminthosporium maydis, Rhizoctonia solani, Botrytis cinerea and Sclerotinia sclerotiorum. Results of antifungal activity analysis indicated that some of the products showed good to excellent antifungal activity, as compound 2 showed excellent activity against G. zeae and R. solani and potent activity against H. maydi, B. cinerea and S. sclerotiorum, and compounds 1, 8 and 10 also displayed excellent antifungal potential against H. maydi, B. cinerea and S. sclerotiorum and good activity against R. solani when compared with the standard carbendazim.