某些3-腙与22-腙胆甾烷芳杂环化合物的合成

甾体类药物由于其特有的生理活性而被广泛应用于各种疾病的治疗。本文采用一锅法及分步合成法,通过胆甾-4-烯-3,6-二酮及22-降-3β-羟基胆甾-5-烯-22醛与水合肼反应,然后进一步与不同的芳香醛反应,合成了5个新的具有不同结构特征的甾体芳杂环腙化合物,合成物经IR、NMR及HRMS进行结构表征。同时对合成物进行了体外抑制肿瘤细胞生长增殖活性测试。     

具有抗肿瘤活性甾体氮芥类化合物的研究进展

本文按照甾体的甾核结构对甾体氮芥化合物进行分类,综述了近年来新合成的甾体氮芥类化合物及其衍生物的抗肿瘤活性及研究进展,并对此方面的发展趋势和应用前景作了展望。     

新型PTP 1B抑制剂喹啉腙及酰腙化合物的合成与活性研究

喹啉腙及喹啉酰腙类化合物具有广泛的生物活性。本文设计合成了29个未见报道的4-(2-芳基)喹啉芳腙和芳酰腙类化合物,采用光吸收检测法测试所合成化合物对蛋白酪氨酸磷酸酶PTP 1B的抑制作用。结果表明,喹啉腙类化合物对PTP 1B具有显著的酶抑制作用,在20μg/mL浓度时,有21个化合物对PTP 1B抑制率在80%以上,其中化合物6q的活性(97.98%)最高。因此,这些化合物具有潜在的调节新陈代谢活性,为发展新的抗糖尿病、抗肿瘤药物提供了一定的研究基础。     

7-位取代的甾体类化合物生物活性研究进展

7-位取代的甾体类化合物是一类具有良好生物活性的化合物,在抗炎、抗肿瘤等领域发挥着重要作用.本文以7-位取代的甾体类化合物为研究对象,按照不同的留体母核进行分类,对近年来有关7-位取代的甾体类化合物的生理活性研究进行综述,并为此类化合物的发展趋势和应用作了展望,以期为抗肿瘤药物的研发提供一定的理论基础.     

具有生物活性氮杂甾体化合物的研究进展

本文概述了近年来新合成的氮杂甾体类化合物的生物活性及研究进展,并对此方面的发展趋势、应用前景做了展望.     

具有特殊甾核结构甾体化合物的合成及生理活性研究进展

改变甾体的甾核结构,在甾核或支链中引入不同的官能团,可以得到一些具有不同生理活性的化合物.按照不同类型甾核结构分类,结合本课题组在具有特殊甾核结构甾体化合物的合成和生理活性研究方面所取得的一些成果,对近年来具有A-失碳甾体化合物、B-失碳甾体化合物及C-失碳-D-增碳甾体化合物的合成及生理活性进行讨论,并展望了此类化合物的发展趋势及应用前景.     

新型甾体N,N-二甲基缩氨硫腙类化合物的合成及其抗肿瘤活性

以乙醇（或甲醇为溶剂）,冰醋酸为催化剂,去氢表雄酮、孕烯醇酮、雌酮和3,5-二羟基-6-甲酰基-B-降胆甾烷分别与N,N-二甲基硫代氨基脲经缩合反应,合成了4个新型的具有不同甾核结构特征的甾体N,N-二甲基缩氨硫腙类化合物（1～4）,其结构经¹H NMR, ¹³C NMR, IR和HR-EI-MS表征。采用MTT法测定了1~4对肝癌细胞(HepG)、人鼻咽癌细胞(CNE-2)和人肾上皮细胞（HEK-293T）的体外抑制细胞生长增殖活性。结果表明：1~3对HepG和CNE-2具有明显的抑制活性。     

具有生理活性甾体肟类化合物的研究进展

按照肟基在甾核中的不同取代位置进行分类,对国内外近年来有关甾体肟类化合物及其衍生物的合成、生理活性研究中具有代表性的工作进行了综述,并对此方面的发展趋势、应用前景作了展望.     

甾体肟醚化合物的合成及抗肿瘤活性研究

肟醚类化合物往往表现出很好的杀虫、除草、抗菌、抗病毒以及抗肿瘤等生理活性,因而受到人们的广泛关注.从胆甾醇、豆甾醇出发,通过不同的合成路线,制备得到系列3-取代、6-取代及22-取代甲氧基肟醚和苄氧基肟醚甾体化合物,通过IR、NMR及MS等现代分析方法对合成物进行了结构表征.同时,分别采用人胃癌细胞(SGC-7901)、人肝癌细胞(Bel-7404)和鼻咽癌细胞(CNE-2)对合成产物及部分合成中间体进行了体外抑制肿瘤细胞生长增殖活性研究.结果表明,某些具有22-取代结构的甲氧肟醚及苄氧肟醚甾体化合物对这些肿瘤细胞株表现出较好的抑制活性,其中22-降-3β-羟基-22-苄氧肟基-豆甾-6-缩胺硫腙(15)对人鼻咽癌细胞CNE-2的IC50值为5.7μmol/L.     

对苯双酰腙类化合物的合成与表征

以对苯二甲酸为起始原料,设计合成了5个新型的对苯双酰腙类化合物,其结构经1H NMR,MS和元素分析表征。     

Novel Steroidal (6R)‐Spiro‐1,3,4‐thiadiazoline Derivatives as Anti‐bacterial Agents

Novel steroidal (6R)‐spiro‐1,3,4‐thiadiazoline derivatives have been synthesized by the cyclization of steroidal thiosemicarbazones. Thiosemicarbazones have been synthesized by the reaction of steroidal ketones with thiosemicarbazide. All the compounds have been characterized by IR, ¹H NMR, mass and elemental analyses. The antibacterial activities of these compounds have been first tested in vitro by the disk diffusion assay against two Gram‐positive and two Gram‐negative bacteria, and then the minimum inhibitory concentration (MIC) values have been determined with the reference of standard drug amoxicillin. The results showed that steroidal thiadiazoline derivatives exhibited better antibacterial activity than the steroidal thiosemicarbazone derivatives. Chloro and acetoxy substituents on the 3β‐position of the steroidal thiadiazoline ring increased the anti‐bacterial activity. Among all the compounds, compounds 7 and 8 were found better inhibitors as compared to the respective drug amoxicillin.     

新型甾体缀合物的设计合成及活性研究*

甾体化合物是一类生物体中广泛存在并起重要功能的生物分子。其特殊结构使这类化合物具有亲脂性,膜亲合性以及与低密度脂蛋白的特异性结合等性能。利用这些特性设计合成各种药物分子的甾体缀合物,可增加药物分子的脂溶性,提高跨膜渗透能力,在特定组织中的分布以及甾体缀合物自身具有独特的生物活性,对探索新型生物活性分子具有重要意义。本文介绍了近年来在设计合成新型甾体缀合物领域的研究进展,包括甾体药物缀合物、含磷甾体缀合物、作为离子通道和分子载体的缀合物及甾体二聚缀合物等。     

呋喃甾烷型皂甙的研究进展

综述了呋喃甾烷型皂甙(双糖链甾体皂甙)的结构特点、化学性质、生理活性和生源合成。列举了1966～1999年发现的双糖链甾体皂甙,共214个。     

具有生理活性的甾体酰胺类化合物

在甾体的甾核或支链上引入不同的官能团后可得到不同生理活性的化合物,它们有可能会成为人类治疗不同疾病的药物,因此甾体药物除了作为传统激素类药物使用外,在抗肿瘤药物、抗炎药物中的应用也成为甾体的重要研究内容之一。含有酰胺官能团的甾体化合物具有很好的生物活性。本文按照酰胺基团在甾体酰胺化合物中的位置进行分类,同时结合本课题组在甾体酰胺化合物的合成和生理活性研究方面所取得的一些成果,概述了近几年来新合成及发现的甾体酰胺类化合物及其衍生物的生理活性及研究进展,包括作为抗肿瘤药物的甾体酰胺化合物的设计、筛选、对5α-还原酶的抑制作用、抑制肿瘤细胞生长增殖活性及抗菌作用,并对此方面的发展趋势、应用前景作了展望。     

25R/25S stereochemistry of spirostane‐type steroidal sapogenins and steroidal saponins via chemical shift of geminal protons of ring‐F

A method based on the differences among the ¹H NMR chemical shifts of geminal protons of ring‐F methylene resonances (H₂‐23, H₂‐24 and H₂‐26) is proposed for ascertaining the 25R/25S stereochemistry of ring‐F unsubstituted spirostane‐type steroidal sapogenins and steroidal saponins. Copyright © 2003 John Wiley & Sons, Ltd.     

Purification of the total steroidal saponins from fenugreek seeds (Trigonella foenum-graecum L.) using aqueous two-phase system and determination of diosgenin content using micellar electrokinetic chromatography method

The total steroidal saponins, particularly its major steroidal sapogenin (diosgenin), are the main active principles of fenugreek seed extract. In this study, an ethanol-salt aqueous two-phase system (ATPS) was explored for the purification of the total steroidal saponins, and the process conditions were optimized by response surface methodology (RSM). Under the optimized conditions, the RSM predicted recovery of the total steroidal saponins in the top phase of ATPS was 97.9%, which agreed with the average experimental recovery (98.3 ± 4.2% (n = 6)). Moreover, a rapid micellar electrokinetic chromatography (MEKC) method was developed for the determination of diosgenin from extracts. The diosgenin content in the ATPS top phase extract was 3-fold higher than that in crude extract, suggesting this ATPS having a great potential for purification pharmacological active ingredients from fenugreek seeds.     

Analysis of steroidal glycoalkaloids and their metabolites in Solanum nigrum fruits based on liquid chromatography-tandem mass spectrometry and molecular networking

Solanum nigrum fruit is like a treasure house for anticancer drugs because of its steroidal alkaloids. However, the clinical treatment of cancer mainly uses immature fruits, which can cause a toxic reaction if eaten directly, while mature fruits are eaten as fruit. In order to clarify the reasons for the differences in pharmacodynamics and toxicity between them, we studied the composition and metabolism of steroidal alkaloids in fruits of different maturities based on liquid chromatography-tandem mass spectrometry and molecular networking. As a result, 114 steroidal glycoalkaloids were identified. During fruit ripening, the aglycones of steroidal alkaloids mainly undergo hydroxylation and carboxylation, and the sugar side chains mainly undergo acylation and glycosylation reactions. Furthermore, 219 steroidal alkaloids were identified in a metabolism experiment in rats. Metabolic processes include deglycosylation, redox, sulfuric acid binding, acetyl binding, and glucuronic acid-binding. Steroidal alkaloids in mature fruits have high molecular weight and polarity, which are difficult to absorb, and most of them are excreted through feces and urine, which may be the reason for their poor efficacy. This study lays a foundation for research on the biosynthesis of steroidal alkaloids and provides potential candidates for the discovery of new steroidal alkaloid anticancer drugs.     

Peculiar side-chain fission of steroidal glycosides

The characteristic novel steroidal glycosides of the 23,26-oxygenated spirostanol-type and 16,22-dicarbonyl cholestanol-type obtained in our laboratory underwent the peculiar reactions of side-chain fission between C-22 and C-23 of the steroidal skeleton by acid or alkaline hydrolysis. These reactions would be applied to the structural determination of these sorts of glycosides and suggest the biogenetic pathway of the occurrence of C-22 lactone-type glycosides.     

New stigmastane type of steroidal glycosides from the roots of Vernonia cumingiana

Two new stigmastane type of steroidal glycosides, vernoniacums A and B (1 and 2), with a △7,9(11) steroidal core were isolated from the roots of Vernonia cumingiana. Their structures were elucidated based on various spectroscopic techniques, including IR, HR-FAB-MS, and 1D and 2D NMR. Both compounds were evaluated for their cytotoxicity against HeLa and HCT-8 cells, and compound 1 showed mild activity against the tested cell lines with IC50 values of 15.8 and 35.7 pounds were evaluated for their cytotoxicity against HeLa and HCT-8 cells, and compound 1 showed mild activity against the tested cell lines with IC₅₀ values of 15.8 and 35.7 μM, respectively.     

Steroidal Glycosides from Allium tuberosum Seeds and Their Roles in Promoting Testosterone Production of Rat Leydig Cells

A systematic phytochemical study on the components in the seeds of Allium tuberosum was performed, leading to the isolation of 27 steroidal glycosides (SGs 1–27). The structures of SGs were identified mainly by nuclear magnetic resonance and mass spectrometries as well as the necessary chemical evidence. In the SGs, 1–10 and 22–26 are new steroidal saponin analogues. An in vitro bioassay indicates that 1, 2, 7, 8, 10, 13–15, 20, 23, and 26 display promotional roles in testosterone production of rat Leydig cells with the EC₅₀ values of 1.0 to 4.5 μM, respectively.