Synthetic Chalcone Derivatives as Inhibitors of Cathepsins K and B,and Their Cytotoxic Evaluation

A series of chalcone derivatives, 1 – 15 , were prepared by Claisen? Schmidt condensation and evaluated for their cytotoxicities on tumor cell lines and also against proteolytic enzymes such as cathepsins B and K. Of the compounds synthesized, (E)‐3‐(3,4‐dimethoxyphenyl)‐1‐phenylprop‐2‐en‐1‐one ( 12 ), (E)‐3‐(4‐chlorophenyl)‐1‐phenylprop‐2‐en‐1‐one ( 13 ), (E)‐3‐(4‐methoxyphenyl)‐1‐phenylprop‐2‐en‐1‐one ( 14 ), and (E)‐3‐(4‐nitrophenyl)‐1‐phenylprop‐2‐en‐1‐one ( 15 ) showed significant cytotoxicities. The most effective compound was 15 , which showed high cytotoxic activity with an IC₅₀ value lower than 1 μg/ml, and no selectivity on the tumor cells evaluated. Substituents at C(4) of ring B were found to be essential for cytotoxicity. In addition, it was also demonstrated that some of these chalcones are moderate inhibitors of cathepsin K and have no activity against cathepsin B.     

Thermal solvent-free synthesis of novel pyrazolyl chalcones and pyrazolines as potential antimicrobial agents

A novel approach was adopted for the synthesis of series of new pyrazolyl chalcones (3a-c) by the reaction of 5-chloro-3-methyl-1-phenylpyrazole-4-carboxaldehyde (1) with different 5-acetylbarbituric acid derivatives (2a-c) under thermal solvent-free condition. The chalcones were then converted to the corresponding pyrazolines (4a-c) under the same condition in excellent yields. All the synthesized compounds were characterized using elemental analysis and spectral data (IR, ¹H NMR, and mass spectrometry). The synthesized compounds were tested for their antimicrobial activity by disk diffusion assay with slight modifications against Gram-positive, Gram-negative strains of bacteria as well as fungal strains. The investigation of antimicrobial screening revealed that compounds (3a-4c) showed good antibacterial and antifungal activities, respectively. Among the screened compounds, 3b showed more potent inhibitory activity (MIC = 12.5 μg/ml) nearly to that of standard antibiotics ciprofloxacin, griseofulvin and fluconazole.     

Synthesis of a Natural Chalcone and Its Prenyl Analogs – Evaluation of Tumor Cell Growth‐Inhibitory Activities,and Effects on Cell Cycle and Apoptosis

Six prenyl (=3‐methylbut‐2‐en‐1‐yl) chalcones (=1,3‐diphenylprop‐2‐en‐1‐ones), 2 – 7 , and one natural non‐prenylated chalcone, 1 , have been synthesized and evaluated for their in vitro growth‐inhibitory activity against three human tumor cell lines. A pronounced dose‐dependent growth‐inhibitory effect was observed for all prenylated derivatives, except for 7 . The chalcone possessing one prenyloxy group at C(2′), i.e., 2 , was the most active derivative against the three human tumor cell lines (5.9<GI₅₀<7.7 μM ). The majority of compounds caused an increase in percentage of apoptotic cells and/or they interfered with cell cycle distribution in the MCF‐7 cell line.     

Antimicrobial Activities of 3-Amino- and Polyaminosterol Analogues of Squalamine and Trodusquemine

A series of 3-amino- and polyaminosterol analogues of squalamine and trodusquemine were synthesized and evaluated for their in vitro antimicrobial properties against human pathogens. The activity was highly dependent on the structure of the different compounds involved and the best results were obtained with aminosterol derivatives 4b, 4e, 8b, 8e and 8n exhibiting minimum inhibitory concentrations (MICs) against yeasts, Gram positive and Gram negative bacteria at average concentrations of 3.12–12.5 μM.     

Synthesis,Characterization, Antimicrobial Activity,and Docking Studies of New Triazolic Tripodal Ligands

The synthesis and characterization of new N‐donor bitriazolic tripods were reported. The in vitro antibacterial and antifungal activities of these products were screened against fungal strain (Candida pelliculosa) and against four bacterial strains (Micrococcus luteus, Bacillus subtilis, Listeria innocua, and Escherichia coli). Biological data revealed the effect of the chemical structure on antimicrobial activity. Molecular docking studies of some compounds showed that they could act as inhibitors for the biotin carboxylase enzyme.     

Biological nanosilver particles for the protection of archaeological stones against microbial colonization

The inhabitation of microorganisms and their subsequent interaction with mineral matrix of the stone substrate under varied environmental conditions encourages deterioration of stones leading to the loss of strength, durability and aesthetic. This study highlighted the synthesis of nanosilver particles (AgNPs) using the biogenic volatiles of the bacterial strain Nesterenkonia halobia. The antimicrobial activities of AgNPs were evaluated against the gram positive bacterial strain Streptomyces parvullus and fungal strain Apergillus niger. Furthermore, the silver particles were mixed with two types of consolidation polymers and were used to coat the external surfaces of sandstone and limestone blocks. The stones treated with silicon polymer loaded with AgNPs showed an elevated antimicrobial potentiality against A. niger and S. parvullus. Scan electron microscope (SEM) and electron dispersive X-ray spectroscopy (EDX) analysis of treated stones demonstrated the existence of nano-composite structures containing the elemental silver. Polymers functionalized with AgNPs can be used not only as potent biocides but also for the consolidation of the historic monuments and artifacts.     

Syntheses and Biological Activities of Danicalipin A Derivatives

Synthesis of three derivatives of danicalipin A, tetrachloride, trisulfate and a fluorescent probe was achieved through Wittig reaction strategy. Toxicity of the derivatives against brine shrimp (Artemia salina) as also investigated to provide useful information for the biological activity; i) less chloride derivative showed similar toxicity to danicalipin A, ii) the amphiphilic property, a characteristic feature of danicalipin A, was crucial because trisulfate considerably decreased the toxicity and iii) fluorescent derivative kept brine shrimp toxicity of danicalipin A.     

植物精油生物活性作用机理研究进展

植物精油具有多种生物活性,被广泛应用于医疗保健、食品工业、化妆品、农业等多个领域.本文综述植物精油抗菌、抗癌、抑制肿瘤细胞生长、抗氧化、延缓衰老、防治心血管疾病、抗病毒、消炎等多种生物活性的作用机理,并展望植物精油今后研究的重点及突破方向.     

Synthesis,Biological Activity and Action Mechanism Study of Novel Chalcone Derivatives Containing Malonate

A series of novel chalcone malonate derivatives were synthesized and their antibacterial and antiviral activities were evaluated. All target compounds were characterized by spectral data. The results of antimicrobial bioassay showed that one compound (diethyl [3‐(naphthalen‐2‐yl)‐1‐(3‐nitrophenyl)‐3‐oxopropyl]propanedioate) showed excellent antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo), with an EC₅₀ value of 10.2 μg/mL, which is significantly superior to bismerthiazol (71.7 μg/mL) and thiodiazole copper (97.8 μg/mL). At the same time, the mechanism of two compounds was confirmed by scanning electron microscopy. In addition, another compound (diethyl [3‐(naphthalen‐2‐yl)‐1‐(4‐nitrophenyl)‐3‐oxopropyl]propanedioate) showed significant curative activity to tobacco mosaic virus, with a value of 74.3 %, which was superior to 53.3 % of ningnanmycin. The results of microscale thermophoresis also showed that the Kd value of the combination of two compounds with the coat protein of tobacco mosaic virus was 0.211 and 0.166 μmol/L, which was better than 0.596 μmol/L of ningnanmycin. At the same time, the molecular docking of two compounds with tobacco mosaic virus‐coat protein shows that the compound is well embedded in the pocket between the two subunits of tobacco mosaic virus‐coat protein. These results show that chalcone derivatives containing malonate group can be considered as activators in the design of antibacterial and antiviral agents.     

Cytotoxic and Apoptosis‐Inducing Activities of Steviol and Isosteviol Derivatives against Human Cancer Cell Lines

Seventeen steviol derivatives, i.e., 2 – 18 , and 19 isosteviol derivatives, i.e., 19 – 37 , were prepared from a diterpenoid glycoside, stevioside ( 1 ). Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK‐BR‐3) cancer cell lines, nine steviol derivatives, i.e., 5 – 9 and 11 – 14 , and five isosteviol derivatives, i.e., 28 – 32 , exhibited activities with single‐digit micromolar IC₅₀ values against one or more cell lines. All of these active compounds possess C(19)‐O‐acyl group, and among which, ent‐kaur‐16‐ene‐13,19‐diol 19‐O‐4′,4′,4′‐trifluorocrotonate ( 14 ) exhibited potent cytotoxicities against four cell lines with IC₅₀ values in the range of 1.2–4.1 μM . Compound 14 induced typical apoptotic cell death in HL60 cells upon evaluation of the apoptosis‐inducing activity by flow‐cytometric analysis. These results suggested that acylation of the 19‐OH group of kaurane‐ and beyerane‐type diterpenoids might be useful for enhancement of their cytotoxicities with apoptosis‐inducing activity.     

具有拮抗无乳链球菌能力乳杆菌的筛选及抑菌特性

目的 从罗非鱼(Nile tilapia)肠道中筛选出具有抑菌作用的乳杆菌,测定其对无乳链球菌(Streptococcus agalactiae)的抑菌效果,分析乳杆菌抑制无乳链球菌的有效成分,并利用分子生物学手段对筛选的乳杆菌菌种进行鉴定。 方法 采用双层平板法对具有抑制无乳链球菌的乳杆菌进行筛选,牛津杯法对抑菌效果进行测定,酶蛋白敏感性测定、热处理、有机酸处理等方法分析抑菌活性物质有效成分,16S rDNA分子标记对乳杆菌进行鉴定。 结果 从罗非鱼肠道中筛选出14株乳杆菌,其中菌株RS2对无乳链球菌具有明显的抑菌效果;不同蛋白酶种类、pH处理对乳杆菌无细胞培养液均有不同的影响,经80 ℃处理的乳杆菌无细胞培养液,其抑菌效果未显著改变(t=0.169 2,P=0.873 8)。此外,此株乳杆菌对猪霍乱沙门菌(Salmonella choleraesuis)、大肠埃希菌(Escherichia coli)、金黄色葡萄球菌(Staphylococcus aureus)和志贺菌(Shigella sp.)等病原菌具有良好的抑制作用。经鉴定,该乳杆菌为植物乳杆菌(Lactobacillus plantarum)。 结论 从罗非鱼肠道中分离得到的植物乳杆菌菌株RS2对无乳链球菌等致病菌具有一定的抑制作用,推断其抑菌有效成分为细菌素类物质。此项研究对开发抗生素替代产品,提高食品的品质具有一定价值。     

Synthesis and Biological Activities of New 1,2,4-Triazol-3-one Derivatives

New 2-phenacyl-1,2,4-triazol-3-ones were obtained by the reaction of 5-alkyl-1,2,4-triazol-3-ones with α-bromoacetophenone in an alkaline medium. Selective reduction of the side chain carbonyl group to hydroxy group was achieved with NaBH₄. The reaction of some compounds containing a phenolic hydroxyl with 4-toluenesulfonyl chloride or benzyl bromide in the presence of NaOH led to tosylated or benzylated derivatives. The tosylation or benzylation at the alcoholic hydroxyl was carried out in the presence of sodium metal. Some of the newly synthesized compounds revealed an antimicrobial activity; 6 of 14 new compounds that were studied by the National Cancer Institute were found to possess antitumor activity.__________Translated from Bioorganicheskaya Khimiya, Vol. 31, No. 4, 2005, pp. 430–440.Original Russian Text Copyright ¢ 2005 by N. Demirbas, A. Demirbas, Karaoglu.The text was submitted by the authors in English.     

Antifungal Activities of Four Fatty Acids against Plant Pathogenic Fungi

The effect of the fatty acids linolenic acid, linoleic acid, erucic acid and oleic acid on the growth of the plant pathogenic fungi Rhizoctonia solani, Pythium ultimum, Pyrenophora avenae and Crinipellis perniciosa were examined in in vitro studies. Linolenic and linoleic acids exhibited activity against all of the fungi. However, whereas linolenic acid reduced mycelial growth of R. solani and C. perniciosa at 100 microM, the concentration had to be increased to 1000 microM before any effect on mycelial growth of P. ultimum and P. avenae was observed. Linoleic acid only reduced mycelial growth of R. solani, P. ultimum and P. avenae at 1000 microM, but led to a significant reduction in growth of C. perniciosa at 100 microM. In contrast, oleic acid had no significant effect on growth of R. solani or P. avenae, but gave significant reductions in mycelial growth of P. ultimum at 100 microM and reduced growth of C. perniciosa significantly at 1000 microM. All of the fatty acids reduced biomass production by all of the fungi significantly in liquid culture when added to the media at 100 microM. Erucic acid had no effect on fungal growth at any concentration examined. The antifungal activities exhibited by linolenic, linoleic and oleic acids may be useful in the search for alternative approaches to controlling important plant pathogens, such as those examined in this study.     

甜菊苷及其衍生物的生物活性研究进展

甜菊苷是一种常用天然甜味剂,属于四环二萜糖苷类。药理学研究表明,甜菊苷及其水解产物甜菊醇、异甜菊醇和甜菊双糖苷等具有降血糖、降血压、抗炎、抗肿瘤、止泻、抗菌和免疫调节等多种生物活性。综述甜菊苷、甜菊醇、异甜菊醇、甜菊双糖苷及相关衍生物的生物活性研究进展。     

Carbohydrate-Dependent Biological Activities of Glycosylated Human Interferon-β on Human Hepatoblastoma Cells In Vitro

To evaluate the relationship between the sugar chain structure and biological activity, fibroblast-derived glycosylated human interferon-β, Chinese hamster ovary cell-derived glycosylated recombinant human interferon-β and Escherichia coli-derived unglycosylated recombinant human interferon-β were evaluated using human hepatoblastoma cells in vitro. Native fibroblast interferon-β expressed more cell-growth inhibitory action, 2′5′-oligoadenylate synthetase induction, and the inhibition of hepatitis B virus DNA replication than its asialoform and two recombinant interferon-βs. These results showed that the sugar chain structure of human interferon-β affects its biological activity on human hepatoblastoma cells.     

Antitumor‐Promoting Effects and Cytotoxic Activities of Dammar Resin Triterpenoids and Their Derivatives

Nineteen known triterpenoids, 1 – 19 , and one known sesquiterpenoid, 20 , were isolated from dammar resin obtained from Shorea javanica K. & V. (Dipterocarpaceae). One of the acidic triterpenoids, dammarenolic acid ( 1 ), was converted to fourteen derivatives, namely, an alcohol, 21 , an aldehyde, 22 , and twelve L ‐amino acid conjugates, 23 – 34 . Compounds 1 – 34 were examined for their inhibitory effects on the induction of Epstein–Barr virus early antigen (EBV‐EA) by 12‐O‐tetradecanoylphorbol 13‐acetate (TPA) in Raji cells, a known primary screening test for antitumor promoters. All of the compounds tested, except for compounds 4, 5, 12 – 14, 16 , and 17 , showed inhibitory effects against EBV‐EA activation with potencies either comparable with or stronger than that of β‐carotene, a known natural antitumor promoter. In addition, (20S)‐20‐hydroxy‐3,4‐secodammara‐4(28),24‐dien‐3‐al ( 22 ) exhibited inhibitory effects on skin tumor promotion in an in vivo two‐stage mouse skin carcinogenesis test based on 7,12‐dimethylbenz[a]anthracene (DMBA) as initiator, and with TPA as promoter. Furthermore, evaluation of the cytotoxic activities of compounds 1 – 34 against human cancer cell lines showed that reduction (i.e., 21 and 22 ) or conjugation with L ‐amino acids (i.e., 23 – 34 ) of compound 1 enhanced the cytotoxicity against human melanoma cell line CRL1579.     

Synthesis and biological evaluation of novel N-substituted 1H-dibenzo[a,c]carbazole derivatives of dehydroabietic acid as potential antimicrobial agents

A series of new N-substituted 1H-dibenzo[a,c]carbazole derivatives were synthesized from dehydroabietic acid, and their structures were characterized by IR, ¹H NMR and HRMS spectral data. All compounds were evaluated for their antibacterial and antifungal activities against four bacteria (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas fluorescens) and three fungi (Candida albicans, Candida tropicalis and Aspergillus niger) by serial dilution technique. Some of the synthesized compounds displayed pronounced antimicrobial activity against tested strains with low MIC values ranging from 0.9 to 15.6 μg/ml. Among them, compounds 6j and 6r exhibited potent inhibitory activity comparable to reference drugs amikacin and ketoconazole.     

Chemical Composition and Biological Activities of Tunisian Cupressus arizonica Greene Essential Oils

The chemical composition of the essential oils obtained by hydrodistillation of leaves, stems, and female cones of Cupressus arizonica Greene , grown in Tunisia, was studied by GC‐FID and GC/MS analyses. Altogether, 62 compounds were identified, 62 in the leaf oil, 19 in the cone oil, and 24 in the stem oil. The cone and stem oils were mainly composed by monoterpene hydrocarbons (96.6 and 85.2%, resp.). In the leaf oil, the total sesquiterpene fraction constituted 36.1% and that of the monoterpene hydrocarbons 33.8% of the total oil composition. The three oils were evaluated for their in vitro herbicidal activity by determining their influence on the germination and the shoot and root growth of the four weed species Sinapis arvensis L., Lolium rigidum Gaudin , Trifolium campestre Schreb ., and Phalaris canariensis L. At the highest doses tested (0.8 and 1.0 mg/ml), the leaf essential oil inhibited either totally or almost completely the seed germination and the shoot and root growth of S. arvensis and T. campestre. The oils were also tested for their antifungal activity; however, their effects on the fungal growth were statistically not significant.     

海南粗榧内生真菌抗肿瘤抗菌活性的筛选

对72株海南粗榧(Cephalotaxus hainanensis Li)内生真菌进行了抗肿瘤和抗菌活性筛选。结果显示, 有9株内生真菌至少对一种指示瘤株具有细胞毒活性, 5株内生真菌对金黄色葡萄球菌有较强的抑菌活性, 1株内生真菌对辣椒疫霉有抑制作用。这表明海南粗榧内生真菌是寻找有价值的生物活性成分的潜在资源, 其生物活性成分值得进一步研究。     

Synthesis,Characterization, and Anti‐Amoebic Activity of N‐(Pyrimidin‐2‐yl)benzenesulfonamide Derivatives

A new series of N‐(pyrimidin‐2‐yl)benzenesulfonamide derivatives, 3a – 3i and 4a – 4i , was synthesized from pyrimidin‐2‐amines, 2a – 2i , with the aim to explore their effects on in vitro growth of Entamoeba histolytica. The chemical structures of the compounds were elucidated by elemental analysis, FT‐IR, ¹H‐ and ¹³C‐NMR, and ESI mass‐spectral data. In vitro anti‐amoebic activity was evaluated against HM1 : IMSS strain of Entamoeba histolytica. The IC₅₀ values were calculated by using the double dilution method. The results were compared with the IC₅₀ value of the standard drug ‘metronidazole’. The selected compounds were tested for their cytotoxic activities by cell‐viability assay using H9C2 cardiac myoblasts cell line, and the results indicated that all the compounds displayed remarkable >80% viabilities to a concentration of 100 μg/ml.