S-Acyl derivatives of thiosalicylamides having antifungal activity. II]

Some S-acyl derivatives of N-alkylthiosalicylamides [Table I: substances (I leads to XXXI)] were prepared and tested for antifungal activity. The substances, most of which had not been previously reported, were prepared by condensation of 2-mercapto-N-alkylbenzamides with suitable acylating agents. The antifungal activity of the compounds was tested in vitro against Candida albicans and Trichophyton mentagrophytes. For some compounds the was tested activity against the above strains fungicidal, Candida tropicalis and Saccharomyces cerevisiae. Many of the compounds proved to have high antifungal activity comparable with that of Clotrimazol. The results extended knowledge on the structure-antifungal activity relationships of this class of compounds. The compounds with the highest antifungal activity were: 2-acetylmercapto-N,n-heptylbenzamide (XXVIII); 2-acetylmercapto-5-Cl-N,n-propylbenzamide (XIV); 2-acetylmercapto-N,n-octylbenzamide (XXXI); 2-acetylmercapto-N,n-pentylbenzamide (XXV); 2-acetylmercapto-N,n-hexylbenzamide (XXVII).     

S-acylderivatives of thiosalicylamides with antifungal activity. I.]

A series of S-acylderivatives of N-ethylthiosalicylamide (substances I leads to XXIII) was prepared and tested for in vitro antifungal activity. The substances, not previously reported, were prepared by the reaction of 2-mercapto-N-ethylbenzamide with suitable acylating agents. The fungistatic activity of the prepared products was tested in vitro against Candida albicans and Trichophyton mentagrophytes. The results given in Table I show that the S-acylderivatives of N-ethylthiosalicylamides have interesting antifungal activity. From examination of the results (Tables I and II) some information on the structure-activity relationship was obtained. 2-Acetylmercapto-N-ethylbenzamide (I) and 2-propionylmercapto-N-ethylbenzamide (III) proved the most active of the compounds tested.     

S-acyl derivatives of thiosalicylamides and their anti-fungal activity. IV]

Some S-acyl derivatives of N-alkylthiosalicylamides [Table I, II: substances (I leads to XXXIII)] in which the acyl group on S in a carbamic or thiocarbamic N-monosubstituted group were prepared and tested in vitro for antifungal activity. All the substances which are not previously recorded were prepared by condensation of 2-mercapto-N-alkylbenzamides with suitable isocyanates or isothiocyanates. The fungistatic activity of the products prepared was tested in vitro against the two strains: Candida albicans and Trichophyton mentagrophytes. The results (Table I and II) show that the N-monosubstituted S-carbamoyl and S-thiocarbamoyl derivatives of N-monosubstituted amides of thiosalicyclic acid have marked in vitro antimycotic activity. Many derivatives have activity of the same order of magnitude as that of clotrimazole and of these the most active compound is 2-(N-phenylcarbamoylmercapto)-N,n-heptylbenzamide (XXVI).     

The antifungal activity of some thiocyanatoaniline derivatives

A series of derivatives of p-thiocyanatoaniline has been synthesised and tested in vitro for activity against dermatophytes; some structure-activity relationships are discussed. One of the more highly active compounds, 2,6-dichloro-4-thiocyanatoaniline, showed some activity against experimental dermatophyte infections when applied topically, was of low toxicity to animals, and did not sensitise them. In a clinical trial the compound also showed some therapeutic activity but caused skin sensitisation.     

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.     

In vitro antifungal activity of naphthoquinone derivatives

In vitro antifungal activities of naphtoquinone-derivatives, which are constituents of Shikon, roots of Lithospermum erythrorhizon, were investigated against several fungal pathogens. When the biological activity of these compounds was tested against fungi, a wide range of sensitivity was recorded. Shikonin was found to have a stronger than fluconazole against yeast-like fungi: four-fold against Candida krusei (minimal inhibitory concentration (MIC); 4 microg/ml) and two-fold (MIC; 4 microg/ml) against Saccharomyces cerevisiae, though it showed the same potency as fluconazole against C. glabrata. Deoxyshikonin also exhibited four-fold stronger activity against C. krusei (MIC; 4 microg/mi) and three-fold (MIC; 2 microg/ml) stronger against S. cerevisiae. Acetylshikonin and beta-hydroxyisovaleryl shikonin showed lower activities against all fungal pathogens except for C. krusei compared with the standard. Against the filamentous fungus, Trichosporon cutaneum, all naphthoquinones were found to have a range of activity with lower potency than standard. This result provides a rational basis for the clinical use of shikon and shows the possibility of its use in medicinal treatment as an anti-inflammatory agent with antifungal activity.     

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。     

Molecular modeling of a series of pyridinecarboxamidrazone-azole derivatives with antifungal activity

Despite the large number of current antifungals used for treating fungal infections, the increased resistance of these microorganisms over the years has been one of the main and major challenges for medicine in the new century. Thus, it remains necessary to discover novel antifungal agents. The objective of this study was to identify the stereoelectronic features related to the antifungal activity of a series of triazoles and imidazoles derivates with activity against Candida albicans, also pharmacokinetic and toxicity in silico were evaluated to guide the rational design and identification of new antifungal agents. The results showed that features such as maintenance of imidazole ring, the profile of distribution and density of high occupied molecular orbital and conformational aspects in these derivatives were important for the activity and also demonstrate that all the compounds showed good oral bioavailability and low theoretical toxicity profile when compared to antifungals on the market, presenting a promising profile for future in vivo studies.     

Substances with antibacterial and antifungal activity. VII. Synthesis and microbiologic activity of new derivatives of 1,5-diarylpyrrole

The synthesis and antifungal activities of new 1,5-diarylpyrrole derivatives are reported. Antimicrobial data in comparison with pyrrolnitrin show that N-methylpiperazinylamides exhibit very poor activity against Candida albicans and Candida sp. while acid and ester derivatives are inactive. Vice-versa many acid or amide derivatives show interesting antibacterial activity. The results obtained are discussed on the basis of structure-activity relationships.     

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.     

吩嗪类衍生物的抗真菌活性研究

目的 研究吩嗪类衍生物的抗真菌活性.方法 利用微量液基稀释法考察吩嗪类衍生物的体外抗真菌活性;利用棋盘式微量稀释法检测吩嗪类衍生物与氟康唑合用对常见临床耐药菌的抗真菌活性;在菌丝诱导条件下考察吩嗪衍生物对白念珠菌菌丝形成的抑制效果.结果 吩嗪类衍生物单用对临床常见条件致病真菌白念珠菌没有明显抗真菌活性;吩嗪衍生物-17...     

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 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.     

Antibacterial and antifungal compounds. VIII. Synthesis and antifungal activity of pyrrol derivatives similar to trichostatin A

Some p-methylbenzolpyrrole acrylic acids and related compounds were synthesized. The new pyrrole derivatives have structural features in common with trichostatin A, an antifungal antibiotic. The above acids and derivatives were tested against Candida albicans and Candida sp in comparison with miconazole, pyrrolnitrin and amphotericin B and showed very weak antifungal activities. Occasionally some activity was found against a few strains of Candida albicans and against Candida pseudotropicalis.     

Synthesis and antifungal activity of 2-aryl-1,2,4-triazolo[1,5-a]pyridine derivatives

A series of novel antifungal triazole derivatives 2-aryl-1,2,4-triazolo[1,5-a]pyridine 9a-m were synthesized and tested in vitro for their growth inhibitory activities against C. albicans and T. rubrum. The MIC values indicate that the activities of three compounds were superior or comparable to fluconazole against both tested fungi, worthy of further investigation of its antifungal activities.     

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.