奥丙嗪衍生物的合成及其生物活性研究

目的 设计合成一系列NO供体型奥丙嗪，并考察它们的体外NO释放活性与抗炎活性。方法 以奥丙嗪为原料，利用其羧基将奥丙嗪与呋咱环结构或硝酸酯结构偶联起来，得到NO供体型奥丙嗪。结果与结论 合成11个NO供体型奥丙嗪衍生物，其中化合物Ⅰa、Ⅰg和Ⅱa～Ⅱd6个化合物为新化合物，目标化合物的结构经MS和^1H-NMR确认。呋咱环型化合物在体外能有效地释放出NO，大多数化合物仍保持抗炎活性。     

Synthetic derivatives of chrysin and their biological activities

Chrysin is one of flavones constituents of Orocylumineicum vent. It has been a hot spot as a potential chemopreventive agent and as a natural molecule with numerous biological activities such as antioxidant, antitumor, antiviral, anti-hypertension, anti-diabetic, antibacterial, and so on in recent years. Because of its poor solubility, small intestinal absorption, and the rapid metabolism of glycosylation, a large number of efforts had been made by domestic and foreign researchers on designing its analogs and conjugates to obtain compounds with improved efficacy and selectivity for developing more active drugs for clinic. This article reviews the current research of studying on chrysin derivatives including their properties and possible applications. Additionally, this article also presents the basic information concerning chemical reactivity of chrysin, relevant to the synthesis of its derivatives.     

Proflavine/acriflavine derivatives with versatile biological activities

Proflavine derivatives are extremely interesting chemotherapeutic agents, which have shown promising pharmaceutical potential due to their wide range of biological activities. This review summarizes the current state of research into the anticancer, antimicrobial, antimalarial and antileishmanial properties of these attractive compounds. Our attention has focused on new classes of proflavine conjugates, which display significant levels of anticancer activity. Highly promising cytotoxic properties have been identified in proflavine conjugates with imidazolidinones, ureas and thioureas. In particular, proflavine-dialkyldithioureas displayed substantial cytotoxic effect against the human leukemia HL-60 cells with IC₅₀ values from 7.2 to 34.0 μm . As well, palladium complexes with proflavine ligand have important biologic activity. The LC₅₀ values of these complexes were significantly lower than that of cisplatin against the SK-BR-3 cell line.     

Xanthone derivatives: new insights in biological activities

Xanthones or xanthen-9H-ones (dibenzo-gamma-pirone) comprise an important class of oxygenated heterocycles whose role is well-known in Medicinal Chemistry. The biological activities of this class of compounds are associated with their tricyclic scaffold but vary depending on the nature and/or position of the different substituents. In this review, an array of biological/pharmacological effects is presented for both natural and synthetic xanthone derivatives, with an emphasis on some significant studies on structure-activity relationships. The antitumor activity of some xanthones as well as the related targets, particularly PKC modulation studies, is also discussed in detail. Examples of the "hit" compounds involved in cancer therapy, namely DMXAA, psorospermin, mangiferin, norathyriol, mangostins, and AH6809, a prostanoid receptor antagonist, are also mentioned. Finally, a historical perspective of these xanthonic derivatives, their relevance as therapeutic agents and/or their uses as pharmacological tools and as extract components in folk medicine are also highlighted.     

In vitro biological activities of new heterocyclic chalcone derivatives

This work reports the synthesis and characterization of new heterocyclic chalcone derivatives 3(a–j) and in vitro biological evaluation for antiproliferative, antioxidant, antibacterial, antifungal, and antiviral properties. The antiproliferative efficacy and LC₅₀ of the compounds against HepG2 cell lines were determined. The LC₅₀ for 3d was found to be 8 μg/mL. All the compounds exhibited moderate DPPH scavenging activity and moderate to good antimicrobial activity against tested bacterial and fungal strains. Further, the compounds at their respective maximum non-toxic concentrations did not inhibit DNA viruses like buffalopox, camelpox, and goatpox.     

含氟β-咔啉类衍生物的合成及其生物活性

以色氨酸甲酯盐酸盐、三氟乙酸和三苯基膦为原料，在四氯化碳溶剂中用一锅法在β-咔啉母核中引入三氟甲基，并通过酯的氨解反应合成一系列新型含氟．β-咔啉类衍生物，其结构经IR、MS、^1H—NMR和^13C-NMR确证。初步体外活性实验表明，所合成的化合物具有一定的抗肿瘤活性和对单胺氧化酶的抑制活性。     

Structure-activity relationships in quinolone antibacterials: design, synthesis and biological activities of novel isothiazoloquinolones

Over the past years it was found that modification of the 3-carboxylic acid group of quinolones generally produced compounds with a substantial decrease in antibacterial activity. The 3-carboxylic acid moiety together with the 4-carbonyl function are believed to be the most structurally critical sites for this class of compounds to DNA gyrase. The authors have designed and synthesized a series of quinolone analogues in which the 3-carboxylic acid group has been modified. These compounds, 2,3,4,9-tetrahydroisothiazolo[5,4-b]quinoline-3,4-diones, possess biological activities far superior to their parent counterparts. For example, the MICs (microgram/ml) for A-62824 (ciprofloxacin 3-carboxylic acid modified analogue) and ciprofloxacin against some organisms are as follows: S. aureus ATCC 6538P (0.02, 0.2); S. epidermidis 3519 (0.05, 0.2); E. coli Juhl (0.005, 0.01); P. aeruginosa A5007 (0.05, 0.1) and Acinetobacter sp. CMX 699 (0.05, 0.78). This investigation has produced the first successful modification of the 3-carboxylic acid group of quinolones resulting in a series of extremely potent antibacterials. The design and synthesis as well as the biological activities of these new derivatives are described.     

吴茱萸碱类衍生物的生物活性研究进展

吴茱萸碱是一类从传统中药吴茱萸中分离得到的咔啉喹唑啉酮类生物碱,具有抗肿瘤、抗炎、抗肥胖、抗阿尔茨海默病、抗菌、杀虫等作用.近年来,吴茱萸碱因其较低的细胞毒性、广泛的生物活性及优良的理化性质而成为药物研发领域的热点,尤其在抗肿瘤先导化合物的寻找研究中取得了较大的进展.本文将从生物活性、作用机制及抗肿瘤活性相关的衍生物设计合成等方面对吴茱萸碱的研究进展作一综述.     

Preparation of new 7-hydroxyguanine derivatives and their biological activities

We prepared new 7-hydroxyguanine derivatives, 7-hydroxyguanosine 5'-monophosphate and N2-tetrahydropyranyl-7-hydroxyguanine, and compared biological activities of 7-hydroxyguanine derivatives including nucleosides acquired previously. 7-Hydroxyguanine and its nucleotide inhibited the focus formation of Rous sarcoma virus. Antitumor activities of these derivatives against mouse leukemia L1210 were not so different from one another. Anti-proliferative activities of the derivatives on various human cell lines were significantly different from one another.     

N-吲哚烷基哌啶类化合物及其类似物的合成和活性研究

摘 要：目的 以5-羟色胺转运体和5-HT2A受体为靶点,设计合成N-吲哚烷基哌啶类化合物及其类似物,研究它们的体内外生物活性。方法 以苯并五元氮杂化合物为原料,经烷基化反应,再与相应的哌啶或哌嗪类化合物进行缩合制备系列化合物。经5-羟色胺再摄取抑制实验和5-HT_2A受体结合实验进行体外筛选,采用小鼠醋酸扭体法和小鼠热板法对其中优选化合物10c、10e进行体内镇痛活性实验;通过阿片受体结合试验和小鼠急性毒性试验,考察目标化合物作为新型非阿片类镇痛剂的潜在开发价值。 结果与结论 共合成了18个未见文献报道的新化合物, 经高分辨质谱及核磁共振氢谱确证结构。体内外药理研究表明：化合物10c和10e具有较强的5-羟色胺再摄取抑制作用,且与5-HT_2A受体有较高亲和力;10c、10e在两种镇痛模型上均显示出很强的镇痛活性;与阿片μ、δ、κ受体无明显亲和力;毒性较小,具有作为非阿片类新型镇痛剂的开发价值。     

A review on biological activities and chemical synthesis of hydrazide derivatives

There has been considerable interest in the development of novel compounds with anticonvulsant, antioxidant, hormone antagonist, analgesic, anti-inflammatory, antiplatelet, antimalarial, antimicrobial, antimycobacterial, antitumoral, vasodilator, antiviral and anti-trypanosomal activities. Hydrazones possessing an azometine -NHN=CH- proton constitute an important class of compounds for new drug development. Therefore, many researchers have synthesized these compounds as target structures and evaluated their biological activities. These observations have been guiding for the development of new hydrazide derivatives that possess varied biological activities.     

Synthesis and reaction of cyanopyridone derivatives and their potential biological activities

4-Carboxy-3-cyano-6-biphenyl-pyrid-2-one (1) was prepared and then allowed to react with methyliodide, benzenesulphonyl chloride, phenylisothiocyanate, acetic anhydride, o-phenylenediamine, phenylmagnesium bromide and phosphorus pentasulphide affording the corresponding N-substituted pyrid-2-one 2-5, 4-(benzimidazol-2-yl)-pyrid-2-one 7, 2-hydroxy-2-phenyl-1,2-dihydro-pyridine 8 and 2-thiopyridone 9 derivatives, respectively. Treatment of 1 with dimethyl sulphate and phosphorus oxychloride to give 2-methoxy pyridine 12 and 2-chloro pyridine 13 derivatives. Reaction of 13 with amines and hydrazine hydrate afforded 14 and 15, respectively. The structural assignments of the new compounds were based on analytical, spectroscopic measurements and chemical reactions. Some of the obtained compounds showed interesting antibacterial and antifungal activities in vitro.     

Synthesis of some N-substituted indole derivatives and their biological activities.

Acylation of 2,3-diphenyl-5-methoxy-indole using ethyl chloroformate or chloroacetyl chloride in dimethylformamide and sodium hydride yielded the N-substituted derivatives 1 and 2, respectively. While Friedel-Crafts acylation using chloroacetyl chloride afforded di-4,6-chloroacetyl derivative 3, the reaction of the N-chloroacetyl derivative 2 with amines, hydrazines, urea, semicarbazide hydrochloride, thiophenol, benzimidazole-2-thiol, thiosemicarbazide, 2-mercaptoethanol and thioglycolic acid was studied. Several of the compounds were tested for their effect on arterial blood pressure, antiinflammatory and ulcerogenic activities.     

Chemistry and biological activities of caffeic acid derivatives from Salvia miltiorrhiza

Caffeic acid (3,4-dihydroxycinnamic acid), one of the most common phenolic acids, frequently occurs in fruits, grains and dietary supplements for human consumption as simple esters with quinic acid or saccharides, and are also found in traditional Chinese herbs. Caffeic acid derivatives occur as major water-soluble components of Salvia miltiorrhiza, including caffeic acid monomers and a wide variety of oligomers. This review provides up-to-date coverage of this class of phenolic acids in regard to structural classification, natural resources, chemical and biosyntheses, analytical methods and biological activities including antioxidant, anti-ischemia reperfusion, anti-thrombosis, anti-hypertension, anti-fibrosis, antivirus and antitumor properties. Special attention is paid to both structural classification and biological activities. The structural diversity and the pronounced biological activities encountered in the caffeic acid derivatives of S. miltiorrhiza indicate that this class of compounds is worthy of further studies that may lead to new drug discovery.     

Synthesis and biological activities of new Mannich bases of chlorokojic acid derivatives

A novel series of 6-chloromethyl-3-hydroxy-2-substituted 4H-pyran-4-one derivatives were synthesized and tested for their antibacterial, antifungal and antiviral in vitro properties. In the view of activity results, compounds 8–11 (MIC: 8 μg/ml) were more remarkably active against Staphylococcus aureus and Enterococcus faecalis. Compounds 1–7 were highly active against Candida albicans and C. parapsilosis with MIC value of 8 μg/ml. Compound 9 bearing 3-chlorophenyl moiety was determined to be the most active compound against RNA virus PI-3.     

叶绿素衍生物的生物活性研究进展

叶绿素衍生物是近年发展起来一类很有理论研究与药用价值的化合物。本文对叶绿素衍生物生物活性的研究进展情况作一综述,讨论了叶绿素衍生物对肿瘤、肝脏损伤、贫血等疾病的作用。     

Synthesis and biological activities of 2,6-diaryl-3-methyl-4-piperidone derivatives

In the present study, a new series of 2,6-diaryl-3-methyl-4-piperidones was synthesized by Mannich reaction (condensation) of ethyl-methyl ketone, substituted aromatic aldehydes and ammonium acetate. Oximes and thiosemicarbazone derivatives of 2,6-diaryl-3-methyl-4-piperidones were synthesized by reaction with hydroxylamine hydrochloride and thiosemicarbazide respectively. The chemical structures were confirmed by means of IR, 1H-, 13C-NMR and mass spectral data. The compounds were screened for acute toxicity, analgesic, local anaesthetic and antifungal activity. 2-(4-Methylphenyl)-3-methyl-6-(4-chlorophenyl)-piperidin-4-one 2 exhibited the highest analgesic and local anaesthetic activity. The oximes and thiosemicarbazones were completely devoid of analgesic and local anaesthetic activity. 2-(4-Methylphenyl)-3-methyl-6-(4-hydroxyphenyl)-piperidin-4-oxime 21 and 2-(4-methoxyphenyl)-3-methyl-6-(4-chlorophenyl)-piperidin-4-oxime 17 exhibited potent antifungal activity against Aspergillus niger. Antifungal activity against Candida albicans was observed only with 2-(4-dimethylaminophenyl)-3-methyl-6-(4-chlorophenyl)-piperidin-4-oxime 20. 2,6-Diaryl-3-methyl-4-piperidones did not exhibit antifungal property.     

Synthesis and biological activities of 2-amino-thiazole-5-carboxylic acid phenylamide derivatives

In an attempt to develop potent and selective anti‐tumor drugs, a series of novel 2‐amino‐thiazole‐5‐carboxylic acid phenylamide derivatives were designed based on the structure of dasatinib. All compounds were synthesized by a systematic combinatorial chemical approach. Biological evaluation revealed that N‐(2‐chloro‐6‐methylphenyl)‐2‐(2‐(4‐methylpiperazin‐1‐yl)acetamido)thiazole‐5‐carboxamide ( 6d ) exhibited high antiproliferative potency on human K563 leukemia cells comparable to dasatinib. Against mammary and colon carcinoma cells 6d was either inactive (MDA‐MB 231) or distinctly less active (MCF‐7 and HT‐29: IC₅₀ = 20.2 and 21.6 µM, respectively). Dasatinib showed at each cell line IC₅₀ < 1 µM. The results of this structure activity relationship study clearly documented that the pyrimidin‐4‐ylamino core of dasatinib is responsible for the anti‐tumor activity against non‐leukemia cell lines.