Synthesis of acetylated glycosides of hydroxyjuglones and study of their antifungal activity

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 26, No. 6, pp. 31–32, June, 1992.     

苔色酸酯的合成及抗真菌作用的研究

目的合成出一系列苔色酸酯,并测试其抗真菌作用.方法以石花为原料,经丙酮提取得到红粉苔酸,用半合成方法,制备苔色酸酯.以试管内药液稀释法,考察苔色酸酯的抗真菌作用.结果合成出了7个苔色酸酯,其结构经元素分析、IR和ESI-MS等表征;其中5个对常见的浅层致病真菌如絮状表皮癣菌等的最低抑菌浓度范围在20～150 μg·mL-1,4个对深层真菌如申克孢子丝菌等的最低抑菌浓度在40～300 μg·mL-1.结论苔色酸酯对9种致病真菌抑菌作用显著,且效果均优于3,5-二羟基甲苯.     

Mechanisms of the antiaggregation activity of 1,4-naphthoquinone derivatives

The antiaggregation effects of synthetic derivatives of 1,4-naphtoquinone and ionol were studied as compared with the antioxidant properties of the agents. The proportional relationship was shown to exist between the antiaggregation properties of the compounds and their antiradical activity under conditions of the interaction with biosubstrates. The data obtained suggest that the derivatives of 1,4-naphtoquinone with the intramolecular transfer of the charge are promising antiaggregation agents.     

Synthesis of novel 1,4-naphthoquinone derivatives: antibacterial and antifungal agents

A novel series of substituted 1,4-naphthoquinone derivatives was synthesized and evaluated for antibacterial and antifungal activity. The structures of the novel products were characterized by spectroscopic methods. Among the tested compounds, 3a and 9 are the most effective compounds against M. luteum as potent antibacterial and C. tenuis and A. niger as potent antifungal. These two compounds are promising as biologically active compounds.     

Haemolytic activity and nephrotoxicity of 2-hydroxy-1,4-naphthoquinone in rats

The short-term toxicity of 2-hydroxy-1,4-naphthoquinone (lawsone) and 2-methyl-1,4-naphthoquinone (menadione) has been compared in rats. 2-Methyl-1,4-naphthoquinone has been shown previously to cause haemolytic anaemia in animals, and this was confirmed in the present experiment. 2-Hydroxyl-1,4-naphthoquinone was found also to cause haemolysis, in a dose-dependent manner, as reflected by decreased blood packed cell volumes and haemoglobin levels and by histopathological changes in spleen, liver and kidney. With both naphthoquinones, the haemolysis was of the oxidative type, characterized by the presence of Heinz bodies within erythrocytes. Haemolysis was the only toxic change identified in rats dosed with 2-methyl-1,4-naphthoquinone. In contrast, 2-hydroxyl-1,4-naphthoquinone was not only a haemolytic agent but also a nephrotoxin, causing renal enlargement, elevated plasma levels of urea and creatinine and histologically-identified tubular necrosis, largely confined to the distal segment of the proximal convoluted tubules. The relationship between the in vivo toxic effects of these naphthoquinones and previously-reported data on their in vitro cytotoxic action is discussed.     

Synthesis and anti-fungal activity of 5-aminopyrazole derivatives]

4-Thiocyanato-5-amino or acylaminopyrazoles were prepared and their antifungal activity was tested against Candida albicans and Trichophyton mentagrophytes: the 4-thiocyanato-5-aminopyrazoles were the most effective in both tests.     

Reactions of isopropyl-alkylamine with 2,3-dichloro-1,4-naphthoquinone and 2,3-dichloro-1,4-naphthoquinone/acetaldehyde

Isopropyl-alkylamines 2 react with 2,3-dichloro-1,4-naphthoquinone (1) to give red 2-chloro-3-isopropyl-alkylamino-1,4-naphthoquinones 3 and with 2,3-dichloro-1,4-naphthoquinone/acetaldehyde to give blue 2-chloro-3-isopropylalkylamino-vinyl-1,4-naphthoquinones 7. It is evident that the formation of 7 is preferred sterically to the formation of 3. The reaction between 2, 1 and acetaldehyde give also red aminoquinones 3 and blue green 2-chloro-3-(4-isopropylalkylamino-buta-1,3-dienyl)-1,4-naphthoquinone like 11.     

6-(1-Alkenoyloxyalkyl)-5,8-dimethoxy-1,4-naphthoquinone derivatives: Synthesis and evaluation of antitumor activity

Thirty six 5,8-dimethoxy-1,4-naphthoquinone derivatives, which bear unsaturated alkyl side chain with ester bond, were synthesized and tested cytotoxic activity on L1210 cells and antitumor activity against ICR mice bearing S-180 cells. It could be recognized that the cytotoxicities of naphthoquinones with R₁ being methyl and propyl (IV1∼24) were not enhanced by replacing the alkanoyls with alkenoyls. In contrast, the introduction of the alkenoyl moieties on the compounds with R₁=hexyl (IV25∼36) resulted in the enhancement of their cytotoxicities. Replacement of alkanoyl group with an alkenoyl group generally increased the T/C value of the mice bearing S-180 cells.     

Synthesis of 2,3-diaziridinyl-1,4-naphthoquinone sulfonate derivatives as potential antineoplastic agents

A new class of 2,3-diaziridinyl-1,4-naphthoquinone sulfonates (27 compounds) has been synthesized and evaluated as potential antineoplastic agents. The most active compounds, benzenesulfonate 4, p-toluenesulfonate 5, p-methoxybenzenesulfonate 7,8-quinolinesulfonate 17, and 2-thiophenesulfonate 20, in the aromatic sulfonate series, at their optimum daily dosage level of 25 mg/kg X 6, produced 100%, 90%, 75%, 80%, and 100% 50-day survivors, respectively, of L1210 tumor-bearing mice. At a lower optimum daily dosage level of 20 mg/kg X 6, treatments with p-fluorobenzenesulfonate 11 and p-nitrobenzenesulfonate 15 resulted in 100% and 80% 50-day survivors. In the aliphatic sulfonate series, methanesulfonate 21 produced 80% 50-day survivors at a 10 mg/kg daily dosage level X 6. Benzenesulfonate 4, p-fluorobenzenesulfonate 11, 8-quinolinesulfonate 17, and 2-thiophenesulfonate 20 derivatives were also tested in mice bearing the B16 melanoma; these agents gave T/C X 100 values of 180, 182, 219, and 161, respectively, in this neoplastic cell system. Structure-activity relationships of compounds of this class are discussed.     

Synthesis and antimicrobial activity of sulfur-containing glycosides

A synthesis of sulfur-containing glycosides based on interaction of allyl derivatives of acetylated carbohydrates-glucose, maltose, and lactose-with phenylsulfenechloride is described. The bactericidal properties of the resulting compounds were studied. Compounds were found to have different levels of inhibitory activity against microorganisms. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 8, pp. 11–12, August, 2007.     

Structure-activity relationships in the haemolytic activity and nephrotoxicity of derivatives of 1,2- and 1,4-naphthoquinone

Naphthoquinone derivatives are under investigation as potential therapeutic agents. Some such compounds are known, however, to be toxic to both animals and humans. Many naphthoquinone derivatives are haemolytic agents, while others cause necrosis of tubular epithelial cells. In the present study, the short-term toxicity of 16 derivatives of 1,2- and 1,4-naphthoquinone has been examined in rats in order to give information on structure-activity relationships. All the naphthoquinones except one caused haemolytic anaemia, but only hydroxy and amino derivatives were nephrotoxic. Among derivatives of 2-amino-1,4-naphthoquinone, substitution in the 3-position decreased haemolytic activity and abolished nephrotoxicity. Methylation of the hydroxyl group of 2-hydroxy-1,4-naphthoquinone had a similar effect. In contrast, methylation of the amino group of 2-amino-1,4-naphthoquinone increased the severity of both haemolysis and renal damage. Among the 1,2-naphthoquinones tested, the 4-methoxy and 4-amino derivatives were more toxic than the corresponding 1,4-isomers, although 4-methyl-1,2-naphthoquinone was less toxic than 2-methyl-1,4-naphthoquinone. At present, the toxicity of naphthoquinone derivatives cannot accurately be predicted on the basis of their chemical structure. In developing naphthoquinone derivatives for use in humans, toxicological studies in animals should be conducted at an early stage, bearing in mind that clinical studies have shown that humans appear to be particularly vulnerable to the nephrotoxic action of these compounds, and that certain individuals are unusually susceptible to their haemolytic action.     

Stability of hemoglobin and albumin adducts of naphthalene oxide, 1,2-naphthoquinone, and 1,4-naphthoquinone.

Naphthalene is an important industrial chemical, which has recently been shown to cause tumors of the respiratory tract in rodents. It is thought that one or more reactive metabolites of naphthalene, namely, naphthalene-1,2-oxide (NPO), 1,2-naphthoquinone (1,2-NPQ), and 1,4-naphthoquinone (1,4-NPQ) contribute to the tumorigenicity of this chemical. These electrophiles are all capable of covalent binding to macromolecules including DNA and proteins. The stability of cysteinyl adducts of NPO, 1,2-NPQ, and 1,4-NPQ were investigated in both hemoglobin (Hb) and albumin (Alb) of male F344 rats following a single administration of 2 different doses (400 or 800 mg naphthalene per kg body weight). To assess the stability of Alb adducts, we compared the rates of NPO-Alb turnover (half-life of approximately 2 days) and 1,2-NPQ-Alb (half-life of approximately 1 day) to the normal turnover rate of Alb in the rat (half-life = 2.5-3 days). Based on the rapid turnover of these adducts relative to Alb itself, we concluded that they were unstable. However, the stability of Alb adducts was not affected by the dose of naphthalene administered (400 or 800 mg/kg). In contrast, NPO-Hb adducts were relatively stable (rate constant of adduct instability 相似文献   

Synthesis and pharmacological activity of difuro-1,4-dihydropyridines

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 23, No. 2, pp. 176–178, February, 1989.