铜绿假单胞菌代谢产物体外对白假丝酵母菌等的抑菌活性研究

目的观察铜绿假单胞菌代谢产物对假丝酵母菌属的体外抑菌活性。方法用交叉条带实验方法测定铜绿假单胞菌对54株假丝酵母菌属的体外抑制活性。结果铜绿假单胞菌产生的抗菌物质对白假丝酵母菌及光滑假丝酵母菌的抑菌作用最强,抑菌带最宽。产蓝绿色素的第6株铜绿假单胞菌对白假丝酵母菌和热带假丝酵母菌的抑制率均达100%,产黄绿色素的第8株铜绿假单胞菌对白假丝酵母菌、热带假丝酵母菌和克柔假丝酵母菌的抑制率也均达100%,铜绿假单胞菌产色素菌株的抗真菌活性优于不产色素的菌株。结论铜绿假单胞菌产生的抗菌物质对白假丝酵母菌、光滑假丝酵母菌具有较强的抗真菌活性。     

In vitro and in vivo anticancer activity evaluation of ursolic acid derivatives

Twenty-three ursolic acid (1) derivatives 2-24 (ten novel compounds 8-10, 14-17 and 22-24) modified at the C-3 and the C-28 positions were synthesized, and their structures were confirmed by IR, ¹H NMR, MS, and elemental analysis. The single crystals of compounds 15 and 17 were obtained. The cytotoxic activity of the derivatives was evaluated against HepG2, BGC-823, SH-SY5Y, HeLa and HELF cells by the MTT assay. The induction of apoptosis and affects on the cell cycle distribution with compound 14 were assessed by fluorescence microscopy, flow cytometry and the activity of caspase-3 in HepG2 cells. Compounds 14-17 had more significant antiproliferative ability against the four cancer cell lines and low cytotoxicity to human embryonic lung fibroblast cells (HELF). Compounds 11, 14-16, 21 and 23 were particularly active against HepG2 cell growth. Compound 14 was selected to investigate cell apoptosis and cell cycle distribution. Flow cytometric analysis and morphologic changes of the cell exhibited that treatment of HepG2 cells with compound 14 led to cell apoptosis accompanied by cell cycle arrest at the S phase in a dose-dependent manner. Furthermore, the activity of the caspase-3 enzyme was increased in the treated cells. In vivo studies using H22 xenografts in Kunming mice were conducted with compound 14 at doses of 50, 100 and 150 mg/kg body weight. The results revealed that the medium dosage group (100 mg/kg) showed significant anticancer activity (45.6 ± 4.3%) compared to the control group.     

In vitro intestinal transport and antihypertensive activity of ACE inhibitory pea and whey digests

Angiotensin I converting enzyme (ACE) inhibitory peptides cause an antihypertensive effect if they reach the systemic circulation. This was investigated for the high ACE inhibitory activity present in peas and whey in vitro gastrointestinal digests. The samples retained high ACE inhibitory activity when incubated in Caco-2 homogenates or rat intestinal acetone powder, both sources of small intestine peptidases. Only little ACE inhibitory activity was transported through Caco-2 cell monolayers in 1 h. As the Caco-2 model is tighter than intestinal mammalian tissue, sufficient absorption of these peptides might occur in vivo. After intravenous administration of 50 mg protein kg(-1) BW in spontaneously hypertensive rats (SHR), pea digest exerted a transient, but strong antihypertensive effect of 44.4 mmHg. Whey digest exerted no effect at this dose. These results suggest that pea digest could be a promising source of ACE inhibitory peptides for use in the prevention and treatment of hypertension.     

In vitro intestinal transport and antihypertensive activity of ACE inhibitory pea and whey digests

Angiotensin I converting enzyme (ACE) inhibitory peptides cause an antihypertensive effect if they reach the systemic circulation. This was investigated for the high ACE inhibitory activity present in peas and whey in vitro gastrointestinal digests. The samples retained high ACE inhibitory activity when incubated in Caco-2 homogenates or rat intestinal acetone powder, both sources of small intestine peptidases. Only little ACE inhibitory activity was transported through Caco-2 cell monolayers in 1?h. As the Caco-2 model is tighter than intestinal mammalian tissue, sufficient absorption of these peptides might occur in vivo. After intravenous administration of 50?mg protein?kg^?1 BW in spontaneously hypertensive rats (SHR), pea digest exerted a transient, but strong antihypertensive effect of 44.4?mmHg. Whey digest exerted no effect at this dose. These results suggest that pea digest could be a promising source of ACE inhibitory peptides for use in the prevention and treatment of hypertension.     

Synthesis and in vitro activity of a series 1beta-methylcarbapenem derivatives

The synthesis of a new series of 1beta-methylcarbapenems having pyrrolidine and piperidine moieties is described. Their in vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of substituent on the pyrrolidine ring was investigated. A particular compound (IIIb) having hydroxypyrrolidine moiety showed the most potent antibacterial activity.     

In vitro antigiardial activity of IRE-6A and IRE-7B, two ethyl-phenylcarbamate derivatives

Resistance is a practical problem associated to the use of benzimidazoles in the antigiardial therapy. Since benzimidazole-resistant strains of fungi have shown increased sensitivity to phenylcarbamates, in this study we synthesized and in vitro tested novel substituted phenylcarbamates against the protozoa Giardia intestinalis. IRE-6A and IRE-7B, two 4-R-ethyl-phenylcarbamates demonstrated an important antigiardial activity although that was modest when compared to albendazole in axenic cultures of Giardia intestinalis. Results of this study suggest a potential role of phenylcarbamates as alternative to benzimidazoles in the therapy of giardiasis.     

In vitro activity of artemisinin, its derivatives, and pyronaridine against different strains of Plasmodium falciparum

The activities of artemisinin (qinghaosu), dihydroartemisinin (dihydroqinghaosu), artemether and pyronaridine were tested in a 48 h in vitro assay against 3 chloroquine-sensitive and one chloroquine-resistant strains of Plasmodium falciparum. Growth inhibition was modelled with a sigmoid Emax model. All compounds markedly inhibited the growth of all strains although, for the chloroquine-resistant strain, merozoites were detected at concentrations as high as 10(-4) M of artemisinin, dihydroartemisinin and artemether. Dihydroartemisinin, artemether and pyronaridine appeared to be more potent than artemisinin, with EC50 values of 4.7-23 nM, 0.98-6.1 nM and 4.4-18 nM respectively, while the EC50 value of artemisinin was 3-108 nM against all 4 strains.     

In vitro antioxidant and enzyme inhibitory properties of Rubus caesius L

The genus Rubus (Rosaceae) has great potential for and a history of use as natural agents in several traditional folk remedies. Based on this concept, this study focused on the antioxidant activities and enzyme inhibitory effects of extracts and fractions from Rubus caesius. Different chemical assays were performed to detect antioxidant capacity, namely, free radical scavenging (ABTS and DPPH assays), reducing power (CUPRAC and FRAP), phosphomolybdenum and metal chelating. Enzyme inhibitory effects were tested towards cholinesterases (AChE and BChE), tyrosinase, α-amylase and α-glucosidase. In addition, total amounts of phenolics and flavonoids were detected by colorimetric assays. Among the samples, the ethyl acetate fraction exhibited the strongest antioxidant potential with its higher concentration of total phenolics. The highest AChE and α-amylase inhibitory activities were observed in the diethyl ether fraction, while the n-butanol fraction had the strongest anti-tyrosinase inhibitor ability. The present study demonstrated that R. caesius may be considered a source of biologically active compounds to develop novel functional products or drugs in the pharmaceutical field.     

Synthesis and inhibitory activity of sialic acid derivatives targeted at viral sialate-O-acetylesterases

A series of sialosides modified at the 4- and 9-hydroxy group were synthesised and tested for inhibition of the viral haemagglutinin-esterase activity from various Orthomyxoviruses and Coronaviruses. While no inhibition of the sialate-4-O-acetylesterases from mouse hepatitis virus strain S or sialodacryoadenitis virus was found, a 9-O-methyl derivative displayed inhibitory activity against recombinant sialate-9-O-acetylesterase from influenza C virus.     

Synthesis and Na+/H+ exchanger inhibitory activity of benzoylguanidine derivatives

Twenty-two compounds of substituted benzoylguanidine derivatives were designed and synthesized as potent NHE1 inhibitors. Twelve compounds showed more potent NHE1 inhibitory activity than cariporide. The activities of compounds 7e, 7h and 7j (IC₅₀ = 0.073 ± 0.021, 0.084 ± 0.012 and 0.068 ± 0.021 nmol/L, respectively) were two orders of magnitude higher than that of cariporide (30.7 ± 2.5 nmol/L). Myocardial cells in vitro screening showed 7j had highlighted protective effect on cardiomyocytes subjected to hypoxia/reoxygenation. Thus it is valuable for further investigation.     

Study of in vitro cytotoxic activity of cyclopentanones derivatives

The cytotoxicity of 30 cyclopentanone derivatives was studied in vitro, in a clonogenic assay using murine leukemia L1210. Results are compared to those obtained with reference medicaments. 17 derivatives exhibit activities against L1210 cells.     

Design, synthesis and AChE inhibitory activity of indanone and aurone derivatives

A new series of indanone and aurone derivatives have been synthesized and tested for in vitro AChE inhibitory activity by modified Ellman method. Most of them exhibit AChE inhibitory activities superior to rivastigmine. Further, the most potent compound 1g was selected to evaluate the effect on the acquisition and memory impairment by mice step-down passive avoidance test.     

In vivo antitumor, in vitro antibacterial activity and alkylating properties of phosphorohydrazine derivatives of coumarin and chromone

The aim of this research was to examine chemical and biological properties of the products (4a-c/5a-c, 8b-c, 9a-b) of the reaction of methyl chromone-3-carboxylate (2), 3-formyl-4-hydroxycoumarin (3), 3-formylchromone (6) and chromone 3-carbonyl chloride (7) with phosphorus hydrazides (1a-c). For structure and keto-enol tautomerism analyses (1)H, (13)C, (31)P NMR spectroscopy was used. The ring transformation species (4a-c/5a-c) containing the coumarin ring (5a-c) were predominant in the solution. The chromone series 8b-c and 9a-b was obtained in reaction of phosphorus hydrazides (1a-c) with 3-formylchromone (6) and chromone-3-carbonyl chloride (7). Alkylating activity of phosphorohydrazides of coumarin and chromone was determined with in vitro Preussmann test (NBP test). Some of the compounds were examined towards antitumor and antibacterial activity. Compounds 4b-c/5b-c and 9a demonstrated in vitro antitumor activity against P388 leukemia. Antineoplastic activity of the compounds 4b/5b and 9a combined with methotrexate was showed using L1210 murine leukemia.     

In vitro inhibitory effect of onion extract on hamster buccal pouch carcinogenesis

In vitro studies were performed that used varying concentrations of onion extract added to cell cultures of an epidermoid carcinoma cell line derived from hamster buccal pouch carcinoma (HCPC-1). The studies demonstrated tumor growth inhibition beginning after 24 hours of incubation at an onion extract concentration of 25% and above in culture media. After 4 days and 10 days of incubation, there was a noted decrease in tumor proliferation. The plating efficiency for 24 hours was observed to produce a 54-89% inhibition in plating density. The results indicated here provide in vitro evidence of the inhibitory and cytotoxic activity on an oral carcinoma cell line.     

In vitro inhibitory effect of onion extract on hamster buccal pouch carcinogenesis

In vitro studies were performed that used varying concentrations of onion extract added to cell cultures of an epidermoid carcinoma cell line derived from hamster buccal pouch carcinoma (HCPC‐1). The studies demonstrated tumor growth inhibition beginning after 24 hours of incubation at an onion extract concentration of 25% and above in culture media. After 4 days and 10 days of incubation, there was a noted decrease in tumor proliferation. The plating efficiency for 24 hours was observed to produce a 54–89% inhibition in plating density. There‐suits indicated here provide in vitro evidence of the inhibitory and cytotoxic activity on an oral carcinoma ceil line.     

利奈唑胺对肠球菌属的体外抗菌活性研究

目的评价利奈唑胺对肠球菌属的体外抗菌活性。方法对2008年1月-2009年10月从临床标本中分离的连续、非重复的186株肠球菌属进行菌种鉴定,并检测其对利奈唑胺等10种抗菌药物的体外抗菌活性,药敏结果导入WHONET 5.4软件进行统计分析。结果 186株肠球菌属中共检出10株耐万古霉素肠球菌(VRE)、14株对万古霉素中介肠球菌,屎肠球菌、粪肠球菌、其他肠球菌VRE的检出率分别为4.8%、1.3%和18.5%;所有菌株对利奈唑胺的敏感率均为100.0%。结论利奈唑胺对肠球菌属具有很高的体外抗菌活性。     

Synthesis and in vitro antiproliferative activity of novel 1-benzhydrylpiperazine derivatives against human cancer cell lines

In order to explore the antiproliferative effect associated with the piperazine framework, several 1-benzhydrylpiperazine derivatives 8(a-d), 9(a-d) and 10(a-h) were synthesized. Variation in the functional group at N-terminal of the piperazine led to three sets of compounds, bearing the sulfonyl, amide and thiourea, respectively. Their chemical structures were confirmed by (1)H NMR, LCMS, IR and elemental analysis. The antiproliferative effect of the compounds were evaluated in vitro using the MTT colorimetric method against one normal cell line (NF-103 skin fibroblast cells) and four human cancer cell lines (MCF-7 breast carcinoma cell line, HepG-2 hepatocellular carcinoma cell line, HeLa cervix carcinoma cell line and HT-29 colon carcinoma cell line) for the time period of 24 h. Among the series, four compounds exhibited interesting growth inhibitory effects against all four cell lines.     

Synthesis and in vitro cysticidal activity of new benzimidazole derivatives

Despite albendazole being the drug of choice in neurocysticercosis treatment, its low solubility limits its bioavailability; therefore, more research is required in order to find new molecules with cestocidal activity and adequate aqueous solubility. A set of 13 benzimidazole derivatives were synthesized and their in vitro activities were evaluated against Taenia crassiceps cysts, using albendazole sulfoxide as reference molecule, showing that two of them exhibited good activity. Molecular modelling revealed that the cysticidal efficacy depends on the presence on the molecule of an H in the 1-position, a planar carbamate group at 2-position, and if the substituent in 5-position is voluminous, it should be orthogonal to the benzimidazole ring.