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排序方式: 共有395条查询结果,搜索用时 25 毫秒
111.
The phosphoinositide 3-kinase (PI3K) signaling pathway is one of the most altered in cancer, leading to a range of cellular responses including enhanced proliferation, survival, and metabolism, and is thus an attractive target for anticancer drug development. Stimulation of the PI3K pathway can be initiated by alterations at different levels of the signaling cascade including growth factor receptor activation, as well as mutations in PIK3CA, PTEN, and AKT genes frequently found in a broad range of cancers. Given its role in glucose metabolism, we investigated the utility of [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG PET) as a pharmacodynamic biomarker of PI3K pathway-induced glucose metabolism. PTEN deletion in human colon carcinoma cells led to constitutive AKT activation but did not confer a phenotype of increased cell proliferation or glucose metabolism advantage in vivo relative to isogenic tumors derived from cells with a wild-type allele. This was not due to the activation context, that is, phosphatase activity, per se because PIK3CA activation in xenografts derived from the same lineage failed to increase glucose metabolism. Acute inhibition of PI3K activity by LY294002, and hence decreased activated AKT expression, led to a significant reduction in tumor [(18)F]FDG uptake that could be explained at least in part by decreased membrane glucose transporter 1 expression. The pharmacodynamic effect was again independent of PTEN status. In conclusion, [(18)F]FDG PET is a promising pharmacodynamic biomarker of PI3K pathway inhibition; however, its utility to detect glucose metabolism is not directly linked to the magnitude of activated AKT protein expression. 相似文献
112.
Mugunthan G Sriram D Yogeeswari P Ravindranathan Kartha KP 《Carbohydrate research》2011,346(13):1760-1766
Chiral nitroimidazoles were synthesized using sugars as the chiral source. The synthesized compounds showed promising antimycobacterial property with MIC value in the range 6.25–12.5 μg/mL against Mycobacterium tuberculosis H37Rv. 相似文献
113.
Senthilkumar K Arunkumar R Elumalai P Sharmila G Gunadharini DN Banudevi S Krishnamoorthy G Benson CS Arunakaran J 《Cell biochemistry and function》2011,29(2):87-95
Urokinase-type plasminogen activator (uPA) is a serine protease that is involved in cancer progression, especially invasion and metastasis including prostate cancer. uPA activation is mediated by transactivation of uPAR and epidermal growth factor receptor (EGF-R) in prostate cancer progression. Prostate cancer (PC-3) cells have highly invasive capacity and they express uPA and uPAR gene. PC-3 cells are treated with quercetin, which inhibits invasion and migration of PC-3 cells. Quercetin downregulates uPA, uPAR and EGF, EGF-R mRNA expressions. Quercetin inhibits cell survival factor β-catenin, NF-κB and also proliferative signalling molecules such as p-EGF-R, N-Ras, Raf-1, c.Fos c.Jun and p-c.Jun protein expressions. But quercetin increased p38 mitogen-activated protein kinase protein expression. Our results suggest that quercetin inhibit migration and invasion of prostate cancer cells. It shows the value for treatment of invasive and metastasis type of prostate cancer. 相似文献
114.
A highly regioselective synthesis of pyrano[3,4-b]indol-1(9H)-ones via gold(III) chloride catalyzed cycloisomerization of 3-ethynyl-indole-2-carboxylic acid was achieved in good to excellent yields. These compounds were screened for their in vitro cytotoxicity against human cervical (HeLa) cell lines. Out of ten compounds, three compounds (7d, 7e and 7j) showed comparable proliferation inhibitory activity against the standard drug cisplatin. Compound 7d was found to be the most efficacious with IC50 value of 0.22 μM. 相似文献
115.
Rajesh SM Kumar RS Libertsen LA Perumal S Yogeeswari P Sriram D 《Bioorganic & medicinal chemistry letters》2011,21(10):3012-3016
The pseudo four-component domino reactions of N-substituted-4-piperidones, substituted aromatic aldehydes and thiourea in the presence of solid sodium ethoxide under solvent-free conditions afforded pyridopyrimidine-2-thiones in almost quantitative yields by simply grinding for 1-2 min. at ambient temperature. The synthesized compounds were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv. Among them, (E)-6-benzyl-8-(2,4-dichlorobenzylidene)-4-(2,4-dichlorophenyl)-3,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidine-2(1H)-thione (MIC 2.8 μM) displays the maximum activity, being 2.7 and 1.7 times more active than the first line antitubercular drugs ethambutol and ciprofloxacin, respectively, and less active than rifampicin and isoniazid, by 28 and 7 times, respectively. 相似文献
116.
Kantevari S Patpi SR Sridhar B Yogeeswari P Sriram D 《Bioorganic & medicinal chemistry letters》2011,21(4):1214-1217
A series of novel aryl and thiophenyl tethered dihydro-6H-quinolin-5-ones have been synthesized in very good yields through CeCl3·7H2O-NaI catalyzed one-pot condensation of β-enaminones derived from the respective methyl ketones; 1,3-cyclohexanedione & 5,5-dimethyl-1,3-cyclohexanedione and ammonium acetate refluxing in 2-propanol. Dihydro-6H-quinolin-5-ones 3a-f was further derivatized to the respective hydroxymethyl analogs using proline as an organocatalyst in aqueous media. Among the all 18 compounds screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB), dihydro-6H-quinolin-5-ones 4e and 4f were found to be most active with MIC 3.13 μg/mL. 相似文献
117.
Suresh Kumar R Ashraf Ali M Osman H Ismail R Choon TS Yoon YK Wei AC Pandian S Manogaran E 《Bioorganic & medicinal chemistry letters》2011,21(13):3997-4000
Hexacyclic derivatives share vital pharmacological properties, considered useful in Alzheimer’s disease. The aim of this study was synthesis and its evaluation for acetyl cholinesterase inhibitory activity of novel hexacyclic analogues. Compound 4f, showed potent inhibitory activity against acetyl cholinesterase enzyme with IC50 0.72 μmol/L. 相似文献
118.
Novel compounds with significant medicinal properties have gained much interest in therapeutic approaches for treating various inflammatory disorders like arthritis, odema and snake bites and the post-envenom (impregnating with venom) consequences. Inflammation is caused by the increased concentration of secretory Phospholipases A(2) (sPLA(2)s) at the site of envenom. A novel compound Tris(2,4-di-tert-butylphenyl) phosphate (TDTBPP) was isolated from the leaves of Vitex negundo and the crystal structure was reported recently. The acute anti-inflammatory activity of TDTBPP was assessed by Carrageenan-induced rat paw odema method. TDTBPP reduced the raw paw odema volume significantly at the tested doses of 50 mg/kg and 70 mg/kg body weight. Molecular docking studies were carried out with the X-ray crystal structures of Daboia russelli pulchella's (Vipera russelli, Indian Russell's viper) venom sPLA(2) and Human non-pancreatic secretory PLA(2) (Hnps PLA(2)) as targets to illustrate the antiinflammatory and antidote activities of TDTBPP. Docking results showed hydrogen bond (H-bond) interaction with Lys69 residue lying in the anti-coagulant loop of D. russelli's venom PLA(2), which is essential in the catalytic activity of the enzyme and hydrophobic interactions with the residues at the binding site (His48, Asp49). Docking of TDTBPP with Hnps PLA(2) structure showed coordination with calcium ion directly as well as through the catalytically important water molecule (HOH1260) located at the binding site. 相似文献
119.
120.
Manavalan Arulmani Kalaichelvan Aparanjini Kalyanasundaram Vasanthi Perumal Arumugam Manavalan Arivuchelvi P. Thangavelu Kalaichelvan 《World journal of microbiology & biotechnology》2007,23(4):475-481
An extracellular thermostable alkaline protease isolated from Bacillus
laterosporus-AK1 was purified by sephadex G-200 gel filtration and DEAE cellulose ion-exchange chromatography techniques. The purified
protease showed a maximum relative activity of 100% on casein substrate and appeared as a single band on SDS-PAGE with the
molecular mass of 86.29 kDa. The protease was purified to 11.1-folds with a yield of 34.3%. Gelatin zymogram also revealed
a clear hydrolytic zone due to proteolytic activity, which corresponded to the band obtained with SDS-PAGE. The protease enzyme
had on optimum pH of 9.0 and exhibited highest activity at 75°C. The enzyme activity was highly susceptible to the specific
serine protease inhibitor PMSF, suggesting the presence of serine residues at the active sites. Enzyme activity strongly enhanced
by the metal ions Ca2+ and Mg2+ and this enzyme compatible with aril detergent stability retained 75% even 1-h incubation. The purified protease remove bloodstain
completely when used with Wheel detergent. 相似文献