4-色满酮曼尼希碱类化合物的合成及其抗血小板聚集活性

4-色满酮类化合物具有广泛的生物活性。为了考察4-色满酮类化合物的抗血小板聚集活性构效关系,笔者设计合成了10种4-色满酮Mannich碱类化合物,其组成和结构经熔点、红外光谱和核磁共振氢谱确证,其中6个(5d～5g,5i～5j)目标化合物均未见文献报道。采用Born's比浊法对目标化合物进行了抗血小板聚集活性的体外筛选,实验结果表明,目标化合物对二磷酸腺苷(ADP)诱导的家兔血小板聚集均具有显著的体外抑制活性。     

3,4-二氢-4-(1-哌啶甲基)-5H-1-苯并氧杂-5-酮盐酸盐的合成及其生物活性研究

α,β-不饱和环戊酮的Mannich碱和α,β-不饱和环己酮的Mannich碱具有显著的抗炎活性,为了寻求新的具有抗炎活性的环酮类化合物,设计了3,4-二氢-4-(1-哌啶甲基)-5H-1-苯并氧杂-5-酮盐酸盐作为目标化合物。以苯酚、γ-丁内酯、甲醛和哌啶等原料合成了目标化合物,并利用熔点、红外光谱、核磁共振氢谱等手段确定了其结构。采用二甲苯致小鼠耳肿胀法,测定了该化合物的抗炎活性,实验结果表明在200mg/kg剂量下该化合物对二甲苯所致小鼠耳肿胀的抑制率为54.5%。采用Born's比浊法测定了该化合物的抗血小板聚集活性,实验结果表明该化合物的抗血小板聚集活性比噻氯匹啶强约23倍。     

色满酮类化合物的合成及其抗炎活性研究

设计合成了4种色满酮类化合物,并利用熔点、红外光谱、核磁共振氢谱等手段确定了其结构。采用二甲苯致小鼠耳肿胀法,测定了该化合物的抗炎活性,实验结果表明在200mg／kg剂量下所合成的3个目标化合物6-[2-（4-吗啉基）乙氧基]色满酮、6-[（喹啉-2-基）甲氧基]色满酮、7-[2-（4-吗啉基）乙氧基]色满酮对二甲苯所致小鼠耳肿胀具有显著的抑制作用。     

新型硫色满酮类化合物的合成及体外抗真菌活性

设计合成9种新型硫色满酮吡唑类化合物,并对其抗真菌活性进行初步评价。首先以取代苯硫酚为起始原料,合成中间体3-次苄基硫色满酮;利用苯甲酰肼与3-次苄基硫色满酮在酸性条件反应生成目标化合物。化合物结构通过核磁共振氢谱、质谱等技术进行确认,抗真菌活性实验表明,9种化合物对部分供试真菌有好的活性。硫色满酮吡唑类化合物在体外的抗真菌活性有待进一步研究。     

3-芳亚甲基色满酮类化合物的研究进展

3-芳亚甲基色满酮是黄酮类化合物中结构较为特殊的一种,在自然界中分布极为有限。该类化合物具有抗氧化、抗真菌、抗感染以及抗突变等广泛生物活性和作用。从天然3-芳亚甲基色满酮的合成方法及其生物活性两方面,综述了该类化合物的研究进展情况。     

含二茂铁基的哒嗪酮类化合物的合成

以二茂铁、丁二酸酐等原料合成了两个含二茂铁基的哒嗪酮类化合物,它们的结构经核磁共振氢谱确证,并对合成的化合物进行了抗血小板聚集活性的体外筛选,有一定的活性。     

香豆素-3-羧酸-烟酸前药的设计、合成及抗血小板聚集活性的研究

设计、合成香豆素-3-羧酸-烟酸前药并研究其抗血小板聚集活性,以发现活性更高的新型抗血小板聚集剂。利用拼合原理,以不同的连接桥将香豆素-3-羧酸和烟酸偶联,合成目标化合物。通过体外抗血小板聚集试验对目标化合物进行抗血小板聚集活性评价。设计、合成了5个新的目标化合物,其结构经ESI-MS、IR及1 H NMR确证。体外抗血小板聚集活性结果表明,目标化合物的抗血小板聚集活性均强于阳性对照药阿司匹林,其中化合物6a的活性最强,值得进一步研究。     

呋喃并[3,2-g]色满类化合物的合成及抗肿瘤活性研究

为了发现新型选择性雌激素受体调节剂,以雷洛昔芬为先导化合物,利用生物电子等排原理以及拼合原理,将雷洛昔芬结构中的苯并噻吩环替换成呋喃并[3,2-g]色满骨架,并进行结构优化,考虑到目标化合物合成的可行性等因素,设计出2-芳酰基-3-芳基呋喃并[3,2-g]色满类化合物作为目标化合物。以7-羟基色满为原料,经过酯化反应和Fries重排后得到6-(4-甲氧基苯甲酰基)-7-羟基色满,进而与取代的α-卤代苯乙酮缩合得关键中间体2-芳甲酰基-3-(4-甲氧基苯基)呋喃并[3,2-g]色满,脱甲基后再与不同氯乙基胺类化合物进行Williamson反应得到目标化合物。所有的10个目标化合物均未见文献报道,其结构经ESI-MS和1H NMR确证。采用MTT法对目标化合物体外抗肿瘤活性进行初步筛选,结果表明,目标化合物7d对人乳腺癌细胞MCF-7、人骨肉瘤细胞U2OS-EGFP-4A12G和人卵巢癌细胞SKOV3具有显著的抑制活性,具有进一步研究价值。     

烃基丹皮酚肟化合物的合成及抗血小板聚集活性

为探究丹皮酚2-位羟基不同烃基取代对抗血小板聚集活性的影响,合成了 7个不同烃基取代的丹皮酚肟衍生物3a～3g并测试了体外抗血小板聚集活性.以丹皮酚为原料,与不同的溴代烃在碱性条件下反应,得到烃基丹皮酚醚,再将其酮羰基肟化,得到7个烃基丹皮酚肟衍生物.目标化合物3a～3g的结构经过红外光谱、核磁共振氢谱和高分辨质谱确证...     

NO供体型丹皮酚衍生物的合成及其生物活性研究

以丹皮酚与溴乙酸为原料制备丹皮酚乙酸,利用其羧基与不同碳数的二溴烷烃反应得到相应的丹皮酚乙酸溴代烷基酯(3a~3e),再与硝酸银反应生成目标化合物NO供体型丹皮酚衍生物4a~4e。目标化合物的结构经过红外光谱、核磁共振氢谱和质谱确证。对合成的NO供体型丹皮酚衍生物进行体外抗血小板聚集及体内调血脂作用的生物活性测试,结果表明,目标化合物均具有一定的体外抗血小板聚集活性及较强的体内降脂作用,其中化合物4c的活性最强。     

7-硝氧烷氧基-3-乙酰基香豆素的合成及抗血小板聚集活性

以间苯二酚为起始原料,经Vilsmeier-Haack反应、Knoevenagel反应得到7-羟基-3-乙酰基香豆素(3),再利用其7位羟基通过连接臂与有机硝酸酯类NO供体耦合,得到5个7-硝氧烷氧基-3-乙酰基香豆素(5a～5e).目标化合物经过红外光谱(IR)、核磁共振氢谱(1H NMR)和高分辨质谱(HRMS)表...     

Synthesis of Analogues of Gingerol and Shogaol,the Active Pungent Principles from the Rhizomes of Zingiber officinale and Evaluation of Their Anti-Platelet Aggregation Effects

The present study was aimed at discovering novel biologically active compounds based on the skeletons of gingerol and shogaol, the pungent principles from the rhizomes of Zingiber officinale. Therefore, eight groups of analogues were synthesized and examined for their inhibitory activities of platelet aggregation induced by arachidonic acid, collagen, platelet activating factor, and thrombin. Among the tested compounds, [6]-paradol (5b) exhibited the most significant anti-platelet aggregation activity. It was the most potent candidate, which could be used in further investigation to explore new drug leads.     

NO供体型烟酸衍生物的合成及其生物活性研究

为寻找活性更强、副作用更小的烟酸前体药物,以烟酸为先导物,设计、合成了5个硝酸酯类NO供体型烟酸衍生物。经红外光谱、核磁共振氢谱及质谱确证了该目标化合物的化学结构。通过体外抗血小板聚集试验、及体内调血脂作用对目标化合物进行生物活性评价。结果表明目标化合物具有较强的体外抗血小板聚集活性及体内良好的降脂作用。     

Antimicrobial and Hypoglycemic Activities of Novel N-Mannich Bases Derived from 5-(1-Adamantyl)-4-substituted-1,2,4-triazoline-3-thiones

The reaction of 5-(1-adamantyl)-4-ethyl or allyl-1,2,4-triazoline-3-thione with formaldehyde solution and various 1-substituted piperazines yielded the corresponding N-Mannich bases. The newly synthesized N-Mannich bases were tested for in vitro inhibitory activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Six compounds showed potent antibacterial activity against one or more of the tested microorganisms, while two compounds exhibited moderate activity against the tested Gram-positive bacteria. None of the newly synthesized compounds were proved to possess marked activity against Candida albicans. The oral hypoglycemic activity of six compounds was determined in streptozotocin (STZ)-induced diabetic rats. Four compounds produced significant strong dose-dependent reduction of serum glucose levels, compared to gliclazide at 10 mg/kg dose level (potency ratio > 75%).     

Analysis of 2-(2-Phenylethyl)chromones by UPLC-ESI-QTOF-MS and Multivariate Statistical Methods in Wild and Cultivated Agarwood

Agarwood is the fragrant resinous material mainly formed from species of Aquilaria. 2-(2-phenylethyl)chromones, especially the highly oxidized 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones, are the main representative compounds from agarwood. It is important to determine whether agarwood in trade is from cultivated trees or natural trees in the Convention on the International Trade in Endangered Species (CITES). We characterized the 2-(2-phenylethyl)chromones in agarwood by ultra-performance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC–ESI-QTOF-MS) and differentiated wild from cultivated agarwood by metabolomic analysis. A total of 141 chromones including 50 potentially new compounds were evaluated as belonging to four structural classes (unoxidized 2-(2-phenylethyl)chromones, 5,6,7,8-tetrahydro-2-(2-phenylethyl)-chromones, bi-2-(2-phenylethyl)chromones, and tri-2-(2-phenylethyl)chromones). The metabolic difference between wild and cultivated agarwood was analyzed by component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Fourteen markers of metabolisms in wild and cultivated agarwood were constructed (e.g., 6,7-dimethoxy-2-(2-phenylethyl)chromone, 6,8-dihydroxy-2-(2-phenylethyl)chromone, 6-methoxy-2-(2-phenylethyl)chromone, etc.). These results indicated that UPLC–ESI-QTOF-MS-based metabonomics analysis in agarwood may be useful for distinguishing wild agarwood from cultivated agarwood.     

LSD1小分子抑制剂的合成及抗肿瘤活性研究

设计并合成了一系列以苯甲酰肼类结构为母核的赖氨酸特异性组蛋白去甲基化酶1(LSD1)小分子抑制剂,并研究其体外抗肿瘤活性。首先,通过体外酶水平单浓度抑制实验进行了初步评价,并随后进一步考察目标化合物对多种LSD1高表达肿瘤细胞株增殖的抑制作用,化合物结构经质谱及核磁共振表征确证。活性评价结果显示,3-(((3R,5S)-3,5-二甲基吗啉代)磺酰基)-N'-(7-羟基-2,3-二氢-1H-茚-1-亚基)苯甲酰肼、N'-(1-(5-氯-2-羟基苯基)亚乙基)-3-(((3R,5S)-3,5-二甲基吗啉代)磺酰基)苯甲酰肼和N'-(4-氯-7-羟基-2,3-二氢-1H-茚-1-亚基)-3-((4-吗啉代哌啶-1-基)磺酰基)苯甲酰肼可显著抑制肿瘤细胞的增殖,并有4个目标化合物对体外多种LSD1高表达的肿瘤细胞株增殖有抑制作用,其中3-(((3R,5S)-3,5-二甲基吗啉代)磺酰基)-N'-(7-羟基-2,3-二氢-1H-茚-1-亚基)苯甲酰肼对BGC823、HCT116、A2780s的半数抑制浓度分别为0.32、0.54、0.90μmol/L。     

Chromones: A Promising Ring System for New Anti‐inflammatory Drugs

The quest for safer anti‐inflammatory drugs is still the focus of several medicinal chemistry programs. Chromones (4H‐chromen‐4‐ones) are a group of naturally occurring compounds ubiquitous in plants, and the chromone core has proven to be a privileged scaffold in medicinal chemistry. Herein we provide an overview of the relevance of chromones as anti‐inflammatory agents, specifically as inhibitors of cyclooxygenase (COX), 5‐lipoxygenase (5‐LOX), interleukin‐5 (IL‐5), and nitric oxide (^.NO) production. Numerous structure–activity relationships and mechanisms of action are discussed. This review is therefore intended to provide a foundation for the design and synthesis of novel chromone‐based compound libraries for further development into safer and more efficient anti‐inflammatory agents.     

含香豆素骨架水杨醛Schiff base荧光材料的制备及光谱性能研究

以间苯二酚和乙酰乙酸乙酯为原料,草酸做催化剂,在无溶剂的条件下,经Pechmann反应催化合成了7-羟基-4-甲基香豆素,再经硝化、还原得到3-氨基7-羟基-4-甲基香豆素。利用3-氨基7-羟基-4-甲基香豆素与水杨醛缩合反应,制备了新型的含香豆素骨架水杨醛Schiff base衍生物,其结构由IR、1HNMR和元素分析确证。通过研究化合物紫外吸收光谱及荧光光谱发现该化合物具有优异光学活性。