天然产物4-O-β-D-葡萄糖-苯并噁唑酮及 4-取代苯并噁唑酮衍生物的合成与活性研究

目的 设计合成天然产物4-O-β-D-葡萄糖-苯并噁唑酮及4-取代苯并噁唑酮类衍生物,并对其抗炎活性、抗乙肝病毒活性进行初步的评价。方法 以2-氨基-间苯二酚为原料,与固体三光气缩合制得4-羟基-苯并噁唑酮,再与溴代糖经过糖苷化反应制得4-取代苯并噁唑酮糖苷类化合物;4-羟基-苯并噁唑酮与酰氯及磺酰氯反应制得4-取代苯并噁唑酮酯类化合物。采用二甲苯致小鼠耳肿胀法测定目标化合物的抗炎活性;采用MTT法测定抗乙肝病毒活性。结果与结论 共合成了10个目标化合物,其中9个化合物未见文献报道,其结构经IR、ESI-MS、¹H-NMR谱确证;活性测试表明,化合物2d、4a、4b具有较好的抗炎活性,化合物2c具有一定的抗乙肝病毒活性。     

含氟咪唑酮系列衍生物的串联合成及其初步药理学研究

目的优化以含氟乙酰丙酸乙酯衍生物为原料一锅法合成3a-三氟甲基-2,3,3a,4-四氢-1H-苯并[d]吡咯[1,2-a]咪唑-1-酮衍生物的方法,并对合成的衍生物进行初步的药理学研究。方法以含氟乙酰丙酸乙酯衍生物与二羰基酯类化合物为原料,通过Claisen酯缩合再脱羧的方法合成3a-三氟甲基-2,3,3a,4-四氢-1H-苯并[d]吡咯[1,2-a]咪唑-1-酮类衍生物。初步药理学研究采用抗戊四唑(pentylenetetrazole,PTZ)实验对大鼠测定药物的抗惊厥活性;采用旋转法测定其神经毒性。结果成功合成5个含氟乙酰丙酸乙酯衍生物,并将其与一系列胺类化合物反应,一锅法合成了22个含氟氮杂双环化合物。初步药理结果显示:2,3,3a,4-四氢-1H-苯并[d]吡咯[1,2-a]咪唑-1-酮的ED50为50μmol/kg,保护指数(protection index,PI)为10.5(PI=TD50/ED50),显示较好的抗惊厥活性。结论本研究优化了反应条件,缩短了反应时间,提高了反应收率,合成的化合物均具有抗惊厥活性和神经毒性。     

4-苯磺酰氧基-苯并口恶唑酮衍生物的合成及其抗炎镇痛作用

目的合成天然产物4-取代苯并口恶唑酮衍生物并对其抗炎镇痛活性进行初步评价。方法以2-氨基间苯二酚为原料,与三光气缩合制得4-羟基-苯并口恶唑酮;以2-取代苯酚为起始物,经取代、重排、氧化反应得到取代苯磺酰氯,取代磺酰氯与4-羟基-苯并口恶唑酮反应制得4-苯磺酰氧基-苯并口恶唑酮酯类化合物。采用二甲苯致小鼠耳肿胀法和小鼠醋酸扭体法测定目标化合物的抗炎及镇痛活性。结果与结论共合成了11个目标化合物,其中10个化合物未见文献报道,目标化合物的结构经ESI-MS、1H-NMR、13C-NMR谱确证;活性实验结果显示,化合物5g具有一定的抗炎活性,化合物5a、5d、5j具有较好的镇痛活性。     

(S)-5-(氮杂环亚甲基)-3-(3-氟-4-吗啉-4-基-苯基)噁唑烷-2-酮衍生物的合成及抗菌活性

目的研究具有抗菌作用的噁唑烷酮衍生物的构效关系。方法由(S)-[3-(3-氟-4-吗啉-4-基-苯基)噁唑烷-2-酮-5-基]-甲醇甲磺酸酯和仲胺的取代反应合成了7个(S)-5-氮杂环亚甲基-3-(3-氟-4-吗啉-4-基-苯基)噁唑烷-2-酮衍生物,其结构通过1HNMR和元素分析或质谱确证。结果所合成的7个化合物对所测的20株细菌均没有明显的体外抗菌活性。结论用氮杂环亚甲基取代吗啉噁酮的5位乙酰胺甲基降低化合物的抗菌活性。     

硒多糖的研究进展

多糖和硒对许多疾病都有防治作用 ,近年来对多糖和硒活性的研究已经较为深入 ,但将多糖与硒有机结合成为硒多糖 ,国内外的研究尚处于起步阶段。硒多糖的化学结构有别于普通多糖 ,形成了特殊的硒氧键 ;硒多糖具有多种生理活性 ,可通过提高相关酶的活性来拮抗重金属中毒和抗活性氧损伤的能力 ,可使癌细胞DNA合成受阻而抑制癌细胞生长等。此文综述了硒多糖的研究进展     

箬叶多糖及其衍生物对小鼠艾滋病作用的研究

目的　研究箬叶多糖及其衍生物硫酸酯多糖和硒酸酯多糖对小鼠艾滋病的治疗作用。方法　采用 Ｌ Ｐ Ｂ Ｍ５ 鼠白血病病毒（ Ｍｕ Ｌ Ｖ） 感染 Ｃ５７ Ｂ Ｌ／６ Ｊ 小鼠的方法建立艾滋病模型。结果　硫酸酯多糖５０ ｍｇ·ｋｇ － １·ｄ － １（ｉｐ） 具有较好地抑制小鼠脾肿大、血清 Ｉｇ Ｇ 增高的作用,硒酸酯多糖在两种给药方式中有一定的保护作用。此外,还首次发现感染小鼠出现 Ｇ Ｓ Ｈ Ｐｘ 活力下降,脂质过氧化产物升高,这与 Ｈ Ｉ Ｖ感染的病人的症状是一致的,硒多糖对提高机体的抗氧化功能有较好的作用。多糖经硫酸酯化、硒酸酯化等化学修饰后,活性有不同程度的提高。结论　作为抗氧化剂和免疫增强剂的微量元素硒和多糖类可能对 Ｈ Ｉ Ｖ 感染的病人有一定的治疗作用     

1,3,4-噁二唑衍生物的合成方法及其抗菌活性研究进展

目的:综述1,3,4-噁二唑衍生物的合成方法及其抗菌活性的研究进展,为开发高效低毒药物提供参考。方法:以"1,3,4-噁二唑""抗菌活性""1,3,4-oxadiazole derivatives""Antimicrobial bioactivity"等为关键词,组合查询1990-2014年中国知网、万方、Pub Med、Science Direct等数据库中有关1,3,4-噁二唑衍生物方面的文献,就其合成方法及抗菌活性等方面的内容进行归纳与总结。结果:共查询到相关文献80余篇,有效文献35篇。目前,除传统合成方法外,还可采用催化法、无溶剂法、聚合物载体法和微波辐射法等新的合成方法制备1,3,4-噁二唑衍生物。经过不同结构改造的含金刚烷基、脂肪酸、磺酰、氰基、吡啶基、苯骈咪唑类的1,3,4-噁二唑衍生物对革兰阴性菌、革兰阳性菌、真菌等均具有一定的抗菌活性。结论:1,3,4-噁二唑是药物化学发展至关重要的先导化合物,其衍生物对致病微生物具有良好的抑制和杀灭作用。分析不同结构改造的1,3,4-噁二唑衍生物的抗菌活性,有助于寻找更加高效、新颖的抗菌药物。     

5-取代苯基,1-氢及1-正丙基吡唑烷酮-3化合物抗惊作用QASR的研究

研究了5-取代苯基吡唑烷酮-3衍生物中苯基取代基的变化对抗惊活性的影响。按照Topliss改进法设计并合成了。1-氢及1-正丙基取代的化合物各六个,找到了活性较强的化合物,为5-(对氟苯基)-1-丙基吡唑烷酮-3,其ED_(50)为14.7mg/kg。经QSAR研究,发现疏水参数∑π对活性影响较大,苯上取代基的立体参数B_4和电性参数Ⅰ×10~2可以改进相关系数r。方程说明5-位苯上引入体积小的吸电子基团可使抗惊活性提高。     

硒化桑葚多糖及其抗氧化活性研究

目的:通过硒化修饰改变桑葚多糖分子结构,并对比研究其体内抗氧化活性.方法:采用水提醇沉法提取桑葚多糖(FMP),硒化修饰FMP,得到桑葚多糖硒化衍生物(FMPs);考察桑葚多糖的体内抗氧化能力,测定小鼠血清和肝脏中MDA、肝脏T-AOC和CAT;建立高脂血症大鼠抗氧化损伤模型,考察FMP及FMPs的抗氧化能力.结果:FMPs及FMP均可以显著提高正常小鼠肝组织CAT活力及T-AOC,降低小鼠血清及肝脏MDA含量,FMPs抗氧化活性明显优于FMP.此外,FMPs及FMP还可以显著降低四氧嘧啶致高脂大鼠的氧化损伤程度,提高其血清SOD活力及肝脏T-AOC,并降低其血清MDA含量.结论:硒化修饰可显著提高桑葚多糖的抗氧化活性.     

伪绵马酚及其衍生物的合成与体外抗真菌作用

目的设计合成伪绵马酚及其衍生物,并考察其抑菌活性。方法基于拼合原理,通过还原、傅-克酰基化等反应合成伪绵马酚及其衍生物并鉴定目标化合物的结构;采用M38-A2微量稀释法测定绵马酚、伪绵马酚及中间体对红色毛癣菌、须癣毛癣菌及犬小孢子菌的抑菌活性。结果与结论合成了伪绵马酚、4个中间体及2个伪绵马酚衍生物;活性研究表明,伪绵马酚对犬小孢子菌、须癣毛癣菌、红色毛癣菌3种皮肤癣菌的抗菌作用最强,其MIC值分别为10、20、28.28 mg·L~(-1)。结论合成的目标化合物对3种受试真菌均具有不同程度的抑制作用,可以为间苯三酚类化合物的成药研究提供理论基础。     

Design,Synthesis, and Monoamine Oxidase Inhibitory Activity of (+)-Cinchonaminone and Its Simplified Derivatives

The absolute structure of an indole alkaloid (+)-cinchonaminone by total synthesis of both (+)-cinchonaminone and its enantiomer was determined. The main focus of the study was the enantioselective synthesis of both enantiomers of a chiral cis-3,4-disubstituted piperidine. We also evaluated monoamine oxidase (MAO) inhibitory activities of these enantiomers. Furthermore, its structurally simplified derivatives were synthesized that did not have any chiral center. Two of these derivatives showed stronger MAO inhibitory activities than that of (+)-cinchonaminone.     

New lipoxygenase inhibitors isolated from Chinese plants. Development of new anti-allergic drugs

Some natural compounds isolated from Chinese plants were found to have strong inhibitory activity for 5-lipoxygenase and were thus able to inhibit leucotriene synthesis. Among these compounds, caffeic acid was selected for study; more than 100 of its derivatives were synthesized and tested for 5-lipoxygenase inhibitory activity. Two derivatives, TMK-919 and TMK-920, proved to be 100 times more potent than the parent compound and were able to inhibit the homologous PCA reaction significantly in rats at a dose of 10 mg/kg, i.v.     

灯盏乙素衍生物的合成及其生物活性

目的为提高灯盏乙素的生物利用度,设计合成了一系列灯盏乙素衍生物,评价其抗脂质过氧化和抗肿瘤的生物活性。方法通过羟乙基化、羟丙基化、酯化反应合成了一系列灯盏乙素衍生物,采用生化法测试部分衍生物对小鼠脑脂质过氧化产物丙二醛(malondialdehyde,MDA)的抑制作用,采用台盼蓝法测试体外抑制白血病细胞HL-60生长活性。结果合成了13个灯盏乙素衍生物,其中7个为未见文献报道的新化合物,其结构经1H-NMR和MS确证;化合物1、13对MDA的抑制作用显著,6-9具有中等强度的抗肿瘤活性。结论灯盏乙素结构中的酚羟基是其抑制脂质过氧化产物MDA的活性基团,葡萄糖醛酸的6-位游离羧基能够增强抗肿瘤活性。     

2H-1-苯并吡喃衍生物的合成及其体外抗癌活性的初步评价

目的设计并合成2H-1-苯并吡喃衍生物化合库并对其体外抗癌活性进行评价。方法以2＇-羟基查耳酮为原料通过微波促进合成得到黄酮衍生物中间体，此中间体与POCl，反应得到4-氯-2H-色原烯-3-醛，通过微波辅助液相平行合成的方法，此醛与ROCONHNH2反应得到2H-1-苯并吡喃衍生物化合库。利用HL-60细胞系评价该化合物库的体外抗癌活性。结果与结论合成了含有32个化合物的2H-1-苯并吡喃衍生物库，体外活性评价表明。部分化合物对HL-60细胞的增殖有一定的抑制作用，其中。化合物9e在浓度为30μmol·L^-1的抑制率为70．8％。     

Synthesis of some quinoxaline derivatives containing indoline-2,3-dione or thiazolidinone residue as potential antimicrobial agents

The synthesis of some quinoxaline derivatives containing indoline-2,3-dione or thiazolidinone residue is described. The synthesized derivatives were screenedin vitro for their growth inhibitory activity against six species of bacteria, viz.Staphylococcus aureus, Streptococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens andMycobacterium semegmatis. Most of the compounds exhibited antimicrobial activity especially those having indoline-2,3-dione moiety.     

Chlorogenic acid derivatives with alkyl chains of different lengths and orientations: potent alpha-glucosidase inhibitors

Alpha-glucosidases play important roles in the digestion of carbohydrates and biosynthesis of viral envelope glycoproteins. Inhibitors of alpha-glucosidase are promising candidates for the development of antitype II diabetics and anti-AIDS drugs. Here, we report the synthesis and alpha-glucosidase inhibitory activity of mono- and diketal/acetal derivatives of chlorogenic acid. The diketal derivatives showed more potent inhibitory activity than the monoketals. The 1,7-(5-nonanone) 3,4-(5-nonanone)-chlorogenic acid diketal showed remarkable inhibitory activity against alpha-glucosidases with potency better than that of 1-deoxynojirimycin hydrochloride. Four diasteremers of pelargonaldehyde diacetal and two of monoacetal derivatives of chlorogenic acid were synthesized in this study. They showed significant potent inhibition similar to or more potent than the ketal counterparts. Acetals with the alkyl chain oriented toward position 2 of chlorogenic acid showed more potent activity than those oriented toward position 6.     

Synthesis of pyrazole-based 1,5-diaryl compounds as potent anti-inflammatory agents

Series of 1,5-diaryl pyrazole ester derivatives have been synthesized and found to contain potent inhibitory activity against cyclooxygenase-2 (COX-2) enzyme. The article describes synthesis of the target pyrazole analogs and biological assay using Carrageenan induced rat paw for investigation.     

2-吲哚醛西佛碱化合物的合成及其抗癌活性研究

目的：合成一系列吲哚-2-位西佛碱衍生物,通过药理筛选寻找具有抗癌活性的化合物。方法：通过亲核取代、还原、氧化、亲核加成等反应得到目的化合物。结果：设计合成了22个吲哚-2-位西佛碱新化合物,药理筛选结果显示2个化合物(5,14)对KB癌细胞株有抑制作用。结论：药理筛选结果表明,一些化合物显示了一定的抗癌活性,值得进一步研究。     

Antimycobacterial evaluation of novel [4,5‐dihydro‐1H‐pyrazole‐1‐carbonyl]pyridine derivatives synthesized by microwave‐mediated Michael addition

The focus of this study is the synthesis and biological activity evaluation of a series of dibenzalaceton derivatives (3a‐3n) and novel [4,5‐dihydro‐1H‐pyrazole‐1‐carbonyl]pyridine derivatives (5a‐5g) against Mycobacterium bovis, Bacillus Calmette–Guerin (BCG). Dibenzalacetone derivatives were synthesized by benzaldehyde derivatives. The [4,5‐dihydro‐1H‐pyrazole‐1‐carbonyl]pyridine derivatives were synthesized by Michael addition reaction and using green chemistry microwave‐mediated method. All compounds were evaluated against BCG and the activity expressed as minimum inhibitory concentration (MIC) in μM. The result showed good activity for all the compounds especially compounds (3a), (3n), and (5a) illustrated high activity (7.03, 8.10 and 5.37 μM, respectively). Copyright © 2014 John Wiley & Sons, Ltd.     

beta-Lactam derivatives as enzyme inhibitors: 1-peptidyl derivatives of 4-phenylazetidin-2-one as inhibitors of elastase and papain

N-Peptidyl substituted azetidin-2-ones were synthesized and evaluated as inhibitors of the serine protease elastase, and the cysteine protease papain. All compounds were synthesized from 4-phenylazetidin-2-one, either from the racemate or from the pure enantiomers. The (S)-enantiomer was prepared by enantioselective synthesis from (S)-beta-phenyl-beta-alanine, while the (R)-enantiomer was obtained by enzymatic resolution with alpha-chymotrypsin. N-Alkylation with bromoacetates introduced a spacer group which, after hydrolysis to the free acid, was acylated with amino acid esters or di- or tripeptide esters. The enzymatic assays proved some derivatives to be effective inhibitors of PPE and/or papain. N-BOC protected amino acid derivatives without a spacer group inhibited PPE reversibly, while derivatives with spacer group showed either weak or no inhibitory properties. On the other hand, papain was inactivated irreversibly by ethyl (RS)-2-oxo-4-phenylazetidin-1-acetate. The highest inhibitory activity against papain was found for the diastereomers of N-(2-oxo-4-phenylazetidin-1-acetyl)-L-alanyl-L-valine benzyl ester, a compound with a spacer group.