三唑衍生物的合成及抗真菌活性研究

目的研究不同结构含氮侧链的引入对三唑醇类化合物体外抗真菌活性的影响.方法根据氮唑类抗真菌药物的作用机制及构效关系设计合成了22个含氮侧链取代三唑醇类化合物,其中18个为新化合物;选择8种真菌为实验菌株,进行体外抑菌活性测试.结果初步体外抑菌实验表明:该类化合物对常见深部致病真菌如:白念珠菌、新生隐球菌、申克氏孢子丝菌、卡氏枝孢霉菌均有较好的抑制活性,其中化合物Ⅱ17体外活性优于氟康唑,与酮康唑相当.结论引入含氮侧链结构可以通过改变目标化合物的脂水分配系数及立体化学特征对该类化合物发挥体外抑菌活性产生影响.     

二苯乙烯衍生物的合成及其抗真菌活性测定

目的设计合成二苯乙烯衍生物,并研究其抗真菌活性和构效关系。方法以紫檀芪为先导化合物,分别保持其A环和B环的结构不变,设计并合成了28个二苯乙烯衍生物,所得产物经~1H-NMR和MS验证了结构。参照CLSI(Clinical and Laboratory Standards Institute)M27A方案,以两性霉素B为阳性对照,DMSO为阴性对照,测定了目标化合物对白色念珠菌属Candida albicans SC-5314、Candida albicans 17#和Candida albicans G5的体外抗真菌活性。结果部分化合物具有良好的抗真菌活性,其中(E)-3,5-二甲氧基-2′-羟基二苯乙烯(PS-18)对3种菌株的最小抑菌浓度分别为3.125、6.25、6.25 mg·L~(-1),优于紫檀芪。结论当保持紫檀芪A环结构不变,改变B环结构得到的化合物抗真菌活性差异较大。当B环的酚羟基在2′位时,化合物PS-18表现出比紫檀芪更强的抗真菌活性;而当紫檀芪B环2′位增加一个甲基后,化合物PS-16仅表现出微弱的抗真菌活性。     

Antibacterial and antifungal agents. IV. Synthesis and antifungal activity of econazole analogs with pyrrole structure

The synthesis of analogues of antifungal econazole with a pyrrole moiety starting from 1-(4-chlorophenyl)-2-(1H-pyrrol-1-yl)ethanone and from 1-(4-chlorophenyl)-2-(1H-pyrrol-1-yl)ethanol is described. Results of antimicrobial screening of the new derivatives in comparison with econazole are also reported.     

Synthesis and antifungal activity of some amidrazone derivatives

The synthesis and in vitro antifungal activity of some pyridincarboxyamidrazone derivatives are described. 2-pyridincarboxyamidrazone derivative (IIa) in comparison with miconazole showed an interesting even if low antimycotic activity.     

Synthesis and antifungal activity of novel triazole derivatives

A series of novel azoles (a–v), which are analogues of fluconazole, have been designed and synthesized as potential antifungal agents by the click reaction. The click reaction approach toward the synthesis of novel 1,2,3-triazolyl linked triazole antifungal derivatives a–v was achieved by Cu(I)-catalyzed 1,3-dipolar cycloaddition of propargylated intermediate 5 with substituted azidomethyl benzene. In addition, the target compounds tested can increase antifungal activity.     

Antibacterial and antifungal agents. XV. Synthesis and antifungal activity of structural analogues of bifonazole and ketoconazole.

The synthesis and antifungal activities of the cis- and trans-1-acetyl-4-[4-[[2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethy l)- 1,3-dioxolan-4-yl]-methoxy]phenyl)piperazines 3 and 4 are reported. Stereochemical assignments to diastereomeric pairs of cis/trans isomers were made on the basis of 1H- and 13C-NMR data. Among test derivatives the best activity was shown by the benzoyl esters of the cis- and trans-[2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3-di oxolan-4- yl]methanols 9 and 10.     

Synthesis and antifungal activity of N-aryl-substituted pimaricin derivatives

Reactions of the tetraene macrolide antibiotic pimaricin with 1-fluorobenzenes resulted in the formation of N-aryl-substituted derivatives. The physicochemical and biological properties of the synthesized pimaricin derivatives were studied. The N-aryl-substituted pimaricin derivatives showed high antifungal activity against a broad spectrum of test cultures. The biological studies showed that the acute toxicity (LD₅₀) of the obtained pimaricin derivatives was half that of the starting antibiotic.     

Synthesis and biological activity of adamantane derivatives. VIII. Adamantyl pyridinecarboxylates

Pharmaceutical Chemistry Journal -     

Synthesis and antifungal and antibacterial activity of hexahydronicotine derivatives

Acylation of hexahydronicotine with anhydrides of dicarboxylic acids yielded amido acids. Reaction of amido acids with amines, ethanol, and hydrazine produced derivatives. Studies of these compounds showed them to have antifungal and antibacterial activity. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 42, No. 4, pp. 24–26, April, 2008.     

Synthesis and antifungal activity of organofluorine derivatives of levorin

Reactions of the polyene macrolide antibiotic levorin with organofluorine alcohols lead to the formation of organofluorine esters. Two organofluorine derivatives of levorin have been synthesized and their physicochemical and biological properties have been studied. These derivatives show high antifungal activity against a large number of test cultures. The acute toxicity (LD₅₀) of levorin derivatives was about half that of the initial antibiotic. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 9, pp. 26–28, September, 2007.     

Synthesis and antifungal activity of some new benzimidazole derivatives

Synthesis and antifungal evaluation of 5-ethoxycarbonyl-2-(substituted-benzyl or phenoxymethyl)benzimidazoles are reported. Structures of the compounds were elucidated with IR-, 1H-NMR-, 13C-NMR-, mass-spectra and elemental analysis. Preliminary results show that none of the synthesized benzimidazole derivatives has antifungal activity at the concentration of 100 micrograms/ml against Candida parapsilosis, Candida stellatoidea, and Candida pseudotropicalis.     

Synthesis and antifungal activity of N-trialkylsilyl derivatives of nystatin

Reactions of the polyene macrolide antibiotic nystatin with trialkylchlorosilanes led to the formation of N-alkylsilyl derivatives. The physicochemical and biological properties of the resulting nystatin derivatives were studied. Organic silicon derivatives of nystatin had high levels of antifungal activity against a wide set of test strains. Biological studies showed that the acute toxicity (LD₅₀) of the resulting nystatin derivatives were 2–3 times lower than that of the initial antibiotic. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 42, No. 6, pp. 15–18, June, 2008.     

新型氮唑类化合物的合成及抗真菌活性研究

目的 设计合成含有1,3,4-二唑侧链的新型氮唑类化合物,并研究其体外抗真菌活性。方法 通过酰化、胺解、环合、亲核取代等多步反应合成了14个未见文献报道的目标化合物,其结构通过¹H NMR、MS确证,选择6种真菌为实验菌株,用微量液体稀释法检测目标化合物的体外抑菌活性。结果 所有目标化合物对实验菌株均有一定的抑制活性,尤其对白念珠菌活性较好。化合物10d、10i、10l、10n对白念珠菌的MIC₈₀值为0.003 9 μg/ml,是伊曲康唑（MIC₈₀：0.062 5 μg/ml）的16倍,是氟康唑（MIC₈₀：0.25 μg/ml）的64倍。结论 1,3,4-二唑侧链结构的引入对化合物的活性有影响,可能是侧链结构中二唑环与苯环能够与靶酶较好地结合,从而提高了化合物的活性。     

新型三唑醇类化合物的合成及抗真菌活性研究

目的以氟康唑为先导化合物,设计合成新的三唑醇类化合物,并研究其抗真菌活性。方法引入较大基团的N,N-二取代侧链结构,合成一系列目标化合物,所有化合物结构均经MS、1H NMR等谱确证;选择8种真菌为实验菌株,测定其体外抗真菌活性,、结果合成了18个未见文献报道的目标化合物,化合物对所选真菌均表现出厂一定的抑菌活性,结论引入较大幕团的N,N-二取代侧链结构对抗真菌活性影响较大。     

Synthesis and antifungal activity of N-benzyl derivatives of amphotericin B

N-Benzyl derivatives of the polyene macrolide antibiotic amphotericin B were formed by reacting it with benzaldehydes and cyanoborohydride under reductive amination conditions. The physicochemical and biological properties of the resulting amphotericin B derivatives were studied. The N-benzyl derivatives of amphotericin B had high antifungal activity against a broad range of test cultures. Biological studies found that the acute toxicity of the amphotericin B derivatives was three times less than for the starting antibiotic. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 7, pp. 20–24, July, 2007.     

Synthesis and antifungal activity of compounds of the pinane series

New terpenyl sulfides of the pinane series have been synthesized from (-)-β-pinene, cis- and trans-verbenols, and myrtenol. Screening for antifungal activity of the monoterpenoids of the pinane series has been carried out. The relationship between the structure and antifungal properties of the synthesized compounds has been established.