Screening of Natural Sources for Antiinflammatory Activity (Review)

Abstract

Biological antiinflammatory drugs used for actue chronic inflammation are described and compared with the synthetic drugs. The review considers studies of the last ten years.     

Novel Aryl-bis-quinolines with Antimalarial Activity In-vivo

Three rationally designed isomeric aryl-bridged bis-quinolines, N¹,N^x-bis(7-chloroquinolin-4-yl)phenylene-1,x-diamines, where x = 2, 3 or 4, i.e. o-, m- and p-substituted analogues respectively, were synthesized and evaluated against Plasmodium berghei in-vivo. The compound with x = 2 had an ID50 of 30 mg kg^?1, whereas the p-substituted analogue (x = 4) was not statistically schizonticidal at either of the two dose levels tested in olive oil-dimethylsulphoxide (5 and 25 mg kg^?1, ID50 = 60 mg kg^?1 approx.). When the delivery vehicle was changed to saline-DMSO, antimalarial potency increased for the p-substituted compound (ID50 17mg kg^?1). In contrast, the m-substituted analogue had marked antimalarial activity (ID50 1.2 mg kg^?1), which compares favourably with that of chloroquine diphosphate (ID50 = 4.3 mg kg^?1). The data presented show that the amino-methylene side chain in amodiaquine can be successfully replaced by a 7-halo-4-aminoquinoline, establishing that carbon bridges containing less than four contiguous carbon atoms can be present within highly active aryl-substituted 4-aminoquinoline antimalarials. These results confirm that the presence of an OH group in the aryl bridge is not necessary for antimalarial activity and substantiate the view that, despite the appearance of resistant strains, new and existing aminoquinolines still have an important role in treating malaria.     

三唑醇类化合物的合成及抗真菌活性

本文根据三唑醇类抗真菌化合物构效关系研究的结果提示,以氟康唑为先导物,设计合成了11个未见文献报道的新三唑醇类化合物,经体外抗真菌活性筛选,以氟康唑为参照物,其中四个化合物表现出良好的抗真菌活性.     

一种查询XML异构数据源的新方法

由于异构数据源存在结构差异和结构不兼容等问题,在其上进行查询是一个挑战.本文根据XML树的特点,对其进行了外延,设计了一种新的XML树的查询方法.通过样式图获得XML树的结点间的语义关系,查询条件可以表示为XML样式图模式,查询不被限定于特定的XML树,给出了基于样式图模式的查询算法.用例说明了该方法如何应用于异构数据源的查询.     

Synthesis of Novel Aminopropylguanidine Derivatives with Potential Antihypertensive Activity

Pharmaceutical Research -     

新型长春西汀-维生素C缀合物的合成及抗氧化活性

目的：合成长春西汀-维生素C缀合物,并考察其生物活性。方法：以长春西汀和维生素C为起始原料,经4步反应制得目标产物长春西汀-维生素C缀合物,并采用DPPH·自由基法测定其体外抗氧化活性。结果与结论：目标产物总产率为15．8％,其结构经IR、^1HNMR、^13CNMR和MS确证。初步体外抗氧化活性研究表明,该化合物具有一定的体外抗氧化活性。     

Synthesis, Antiinflammatory and Antibacterial Activity of Novel Indolyl-isoxazoles

Chalcones were synthesized by reacting indole-3-aldehyde, prepared by Vilsemeir Haack reaction with 4-substituted acetophenone in ethanolic KOH solution. These chalcones were immediately reacted with hydroxylamine hydrochloride in presence of glacial acetic acid as reagent to obtain the corresponding isoxazole derivatives. The synthesized heterocycles were characterized on the basis of physical, chemical tests and spectroscopic data. These compounds were tested for the acute antiinflammatory activity and antibacterial activity using carrageenan-induced rat paw edema method and cup-plate method, respectively.     

新型DTC金属配合物的抗肿瘤活性及构像研究

DTC是一类具有广泛生物活性的化合物。Piperazinedithioformates具有一定的抗肿瘤活性,但其溶解性却较差。本文对一系列新型的DTC金属配合物就人体六种癌细胞系进行了体外抗肿瘤作用研究,发现了两个有较好抗肿瘤活性的化合物;并对SRCu进行构像研究,第一次得到了其稳定构像。     

Design,Synthesis and Fungicidal Activity of Novel Sclerotiorin Derivatives

Sclerotiorin, a chlorine‐containing azaphilone‐type natural product, was first isolated from Penicillium sclerotiorum and has been reported to exhibit weak fungicidal activity. Optimization of the substituents at the 3‐ and 5‐positions of the sclerotiorin framework was investigated with the aim of discovering novel fungicides with improved activity. The design of sclerotiorin analogues involved replacing the diene side chain with a phenyl group or an aromatic‐ or heteroaromatic‐containing aliphatic side chain. The designed compounds were synthesized by cycloisomerization and subsequent oxidation of suitable 2‐alkynylbenzaldehydes, in which a variety of substituents were introduced using a Sonogashira coupling reaction. The structures of these newly prepared compounds were confirmed by ¹H and ¹³C NMR spectroscopy, HRMS and single‐crystal X‐ray analysis. The antifungal activity of the synthesized compounds was evaluated against seven phytopathogenic species. Compounds 3 , 9g and 9h were found to have a broad spectrum of fungicidal activity, and these structurally simpler products can be recognized as lead compounds for further optimization.     

新型细菌卟吩类衍生物的合成及抗肿瘤活性研究

目的 设计、合成新型细菌卟吩类衍生物,并研究其抗肿瘤效果。方法 以细菌卟吩类化合物为原料,经还原、溴化后与2-[4-(羟甲基)苯氧基]乙酸甲酯进行醚化,随后水解得到目标化合物。采用NCI-H460 BALB/c裸鼠移植瘤模型,检测药物在组织中的分布,利用光动力治疗法对目标化合物的抗肿瘤效果进行了研究。结果 合成了1个全新结构的细菌卟吩类衍生物,结构经¹H-NMR、¹³C-NMR、MS和UV确证,目标化合物具有较好的组织分布性,对肿瘤细胞的生长具有较好的抑制作用。结论 细菌卟吩类衍生物结构中引入亲水性基团后,组织选择性及抗肿瘤效果得到了改善,值得深入研究。     

Antimicrobial Activity of Novel C2-Substituted 1,4-Dihydropyridine Analogues

The antimicrobial activity of 3-methyl-5-isopropyl (or ethyl) 6-methyl-4-nitrophenyl-1,4-dihydropyridine-3,5-dicarboxylate derivatives was evaluated. Prokaryotes (bacteria) appeared to be more sensitive to their antimicrobial activity than were eukaryotes (filamentous fungi). The best antibacterial activity was shown by derivative 33, which was able to inhibit the growth of Mycobacterium smegmatis (MIC₃₃ = 9 μg.ml⁻¹), Staphylococcus aureus (MIC₃₃ = 25 μg.ml⁻¹), and Escherichia coli (MIC₃₃ = 100 μg.ml⁻¹). In addition, derivative 4 demonstrated its antibacterial power on the acid-fast bacterial species M. smegmatis and on Gram-positive S. aureus. Focusing on the structure-activity relationship, it appears that the increase in the substituent bulk at the C2 position improved the antibacterial activity of the set of compounds studied. Derivatives 33 and 4, carrying 2-cyano-3-oxo-3-phenylprop-1-en-1-yl and allyliminomethyl groups, respectively, showed significantly higher inhibition activities on all tested microorganisms in comparison with the rest of the derivatives. This enhancement was also in good correlation with different log P values (lipophilicity parameter).     

Synthesis and Antiglycation Activity of Novel S-Carboxyalkyl Derivatives of 2-Thiouracil

Pharmaceutical Chemistry Journal - S-carboxyalkyl derivatives of 2-thiouracil were synthesized and their pharmacological activity was studied. Several of the compounds were characterized by...     

Synthesis and Antitumor Activity of Novel Dibutyltin Carboxylates of Aminoglucosyl Derivatives

In this study, di‐n‐butyltin(IV) oxide was reacted with the amino glucose analog, cis‐4‐[N‐(1′,3′,4′,6′‐tetra‐O‐benzoyl‐2‐deoxy‐glucopyranosyl)imido]‐4‐oxo‐2‐butenoic acid ( 1a ) and o‐[N‐(1′,3′,4′,6′‐tetra‐O‐benzoyl‐2‐deoxy‐glucopyranosyl) carbamoyl] benzoic acid ( 2a ) to give the complexes bis‐{cis‐4‐[N‐(1′,3′,4′,6′‐tetra‐O‐benzoyl‐2‐deoxy‐glucopyranosyl)imido‐4‐oxo‐2‐butenoic acid]‐di‐n‐butyltin} carboxylate ( 1 ) and bis‐{o‐[N‐(1′,3′,4′,6′‐tetra‐O‐benzoyl‐2‐deoxy‐glucopyranosyl) carbamoyl‐benzoic acid]‐di‐n‐butyltin}carboxylate ( 2 ). These two compounds were then characterized by IR, NMR and MS. In vitro tests showed that both compounds have high cytotoxicity in four tumor cell lines (P388, HL‐60, A549 and BEL‐7402). Clonogenic assays demonstrated that both compounds 1 and 2 have hematopoietic cell toxicity at 10^?6 m .     

Synthesis and Antimycobacterial Activity of a Novel Series of Isonicotinylhydrazide Derivatives

A novel series of 14 new isonicotinyl hydrazide derivatives 2a – g , 3a – g containing a 4‐thiazolidinone / 2‐azetidinone nucleus were synthesized by reacting N′‐substituted arylidene / heteroarylidene isonicotinyl hydrazide 1a – g with thioglycollic acid in the presence of dry benzene and with chloroacetyl chloride in the presence of triethylamine, respectively. Structures of all newly synthesized compounds were characterized on the basis of elemental analyses and spectral data (IR and ¹H‐NMR). All the title compounds were tested for their in‐vitro antimycobacterial activity against Mycobacterium tuberculosis H₃₇Rv using Alamar‐Blue susceptibility test, and the activity is expressed as the minimum inhibitory concentration (MIC) in μg/mL. Among the series, compounds 2b , 2g , 3b , and 3g displayed an encouraging antimycobacterial activity profile as compared to that of the reference drugs isoniazid / rifampicin.     

新型青蒿素-苯丁酸氮芥酯的合成及抗肿瘤活性研究

根据药效团拼合原理,设计并合成了结构新颖的青蒿素-苯丁酸氮芥酯,其结构由1H NMR、13C NMR和HRMS-ESI表征确定。体外抗增殖测试显示,青蒿素-苯丁酸氮芥酯对人白血病细胞K562和人白血病耐阿霉素细胞K562/ADR均具有较强的抑制活性,IC50值分别为3.065±0.568和15.173±1.297μmol/L。流式细胞术结果表明,青蒿素-苯丁酸氮芥酯能够阻滞K562和K562/ADR的细胞周期,并诱导细胞凋亡。     

哒嗪酮类新化合物9612的抗血栓作用及其作用机制

研究发现 ,哒嗪酮类化合物 96 12灌胃给药 (i.g)能有效抑制大鼠动 静脉旁路血栓形成 ,对胶原致肺血栓小鼠死亡也有较强的保护作用 .剂量为 75、15 0或 30 0mg/kg时 ,抑制率分别为36 0 4%、45 97%和 78 2 5 % ;保护率分别为 48%、6 4%和 72 % ;96 12 (i.g)剂量为 10 0mg/kg或 2 0 0mg/kg时 ,能使小鼠出血时间明显延长 ,延长率分别为 39 6 %和 76 3 % .放射免疫分析测定结果表明 96 12在终浓度为 1～ 10 0 μmol/L时能使洗涤兔血小板环磷酸腺苷水平明显升高 (P <0 0 0 1) .说明 96 12具有较强的抗血栓作用 ,升高血小板cAMP水平可能是其主要作用机理 .     

新型双核席夫碱化合物的合成及荧光活性研究

以水杨醛与N,N,N',N'-四[2-(2-氨基乙氨基)甲酰基乙基]乙二胺反应合成了一种新型八齿席夫碱配体(H4L)及其锌配合物,通过元素分析1、HNMR、IR、紫外光谱、摩尔电导等手段对配体及其配合物进行结构和组成进行表征。同时在DMSO溶液中测定了该双核席夫碱及其锌配合物的荧光活性。     

Synthesis and Anticancer Activity of Novel Betulinic acid and Betulin Derivatives

A series of novel betulinic acid derivatives 3–11 and betulin derivatives 12–17 were synthesized. The compounds were characterized by the means of ¹H‐ and ¹³C‐NMR spectroscopy as well as mass spectrometry. The compounds have been tested on ten tumor cell lines of different histogenic origin. The most active derivatives, containing a chloroacetyl group on C‐3 in betulinic acid 9 and C‐28 in betulin 15 , were up to ten times more cytotoxic and many fold more selective towards tumor cells in comparison to normal cells (fibroblasts) than betulinic acid. Furthermore, compound 15 was found to possess cell growth inhibition even when treated for a short time on anaplastic thyroid cancer cells (SW1736).