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991.
Sara N. Richter Ilaria Frasson Manlio Palumbo Claudia Sissi Giorgio Palù 《Bioorganic & medicinal chemistry letters》2010,20(3):1202-1204
Simocyclinone D8 (SD8) is known to affect Gram-positive bacteria only. By testing SD8 against several clinical isolates, we showed that SD8 resulted very active against Gram-negative bacteria from clinical specimens, while it was shown inactive against laboratory strains. The activity against the former was in part due to enhanced drug entry. In addition, SD8 appears to share chromosome- and plasmid-mediated resistance mechanisms with fluoroquinolones. 相似文献
992.
Radhakrishnan Mahesh Thangaraj Devadoss Dilip Kumar Pandey Shvetank Bhatt Shushil Kumar Yadav 《Bioorganic & medicinal chemistry letters》2010,20(22):6773-6776
A novel series of quinoxalin-2-carboxamides were designed based on the ligand-based approach, employing a three-point pharmacophore model; it consists of an aromatic residue and a linking carbonyl group and a basic nitrogen. The target new chemical entities were synthesized from the key intermediate, quinoxalin-2-carboxylic acid, by coupling it with various amines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl) and 1-hydroxybenzotriazole (HOBt). The obtained compounds’ structures were confirmed by spectral data. The target new chemical entities were evaluated for their 5-HT3 receptor antagonisms in longitudinal muscle myenteric plexus preparation from guinea pig ileum against 5-HT3 agonist, 2-methyl-5-HT, which was expressed in the form of pA2 value. All the synthesized compounds showed antagonism towards 5-HT3 receptor; based on this result, a structure–activity relationship was derived, which reveals that the aromatic residue in 5-HT3 receptor antagonists may have hydrophobic interaction with 5-HT3 receptor. Regardless of their antagonistic potentials, all the synthesized molecules were screened for their anti-depressant potentials by using forced swim test in mice model; interestingly none of the tested compounds affect the locomotion of mice in the tested dose levels. Compounds with significant pA2 values exhibited good anti-depressant-like activity as compared to the vehicle-treated group. 相似文献
993.
994.
Jhillu Singh Yadav Kamani Satyanarayana Pamu Sreedhar Pabbaraja Srihari Thokhir Basha Shaik Shasi Vardhan Kalivendi 《Bioorganic & medicinal chemistry letters》2010,20(12):3814-3817
The racemic total synthesis of elegansidiol, farnesiferol B, and farnesiferol D has been obtained following a Diels–Alder approach. Gillman addition, cross metathesis reaction are the other key steps involved in the target synthesis. 相似文献
995.
Nafees Ahmed Keyur G. Brahmbhatt Sudeep Sabde Debashis Mitra Inder Pal Singh Kamlesh K. Bhutani 《Bioorganic & medicinal chemistry》2010,18(8):2872-2879
Naturally occurring quinolone alkaloids, buchapine (1) and compound 2 were synthesized as reported in literature and evaluated for anti-HIV potential in human CD4+ T cell line CEM-GFP, infected with HIV-1NL4.3 virus by p24 antigen capture ELISA assay. The compounds 1 and 2 showed potent inhibitory activity with IC50 value of 2.99 and 3.80 μM, respectively. Further, 45 alkylated derivatives of quinoline 2,4-diol were synthesized and tested for anti-HIV potential in human CD4+ T cell line CEM-GFP. Among these, 13 derivatives have shown more than 60% inhibition. We have identified three most potent inhibitors 6, 9 and 23; compound 6 was found to be more potent than lead molecule 1 with IC50 value of 2.35 μM and had better therapeutic index (26.64) as compared to AZT (23.07). Five derivatives 7, 19a, 19d, 21 and 24 have displayed good noticeable anti-HIV activity. All active compounds showed higher CC50 values which indicate that they have better therapeutic indices. 相似文献
996.
Paola Barraja Libero Caracausi Patrizia Diana Anna Carbone Alessandra Montalbano Girolamo Cirrincione Paola Brun Giorgio Palù Ignazio Castagliuolo Francesco Dall’Acqua Daniela Vedaldi Alessia Salvador 《Bioorganic & medicinal chemistry》2010,18(13):4830-4843
In the search for new photochemotherapeutic agents, a series of derivatives of the ring system pyrrolo[3,2-h]quinoline—bioisosters of the angular furocoumarin angelicin—were synthesized through a four-step synthetic approach, in reasonable overall yields. Eight of the synthesized derivatives showed a remarkable phototoxicity against a panel of four human tumor cell lines and a great dose UV-A dependence, reaching IC50 values at submicromolar level. The mode of cellular death photoinduced by pyrrolo[3,2-h]quinolines was evaluated through a series of flow cytometric analysis and other tests were performed to clarify their mechanism of action. 相似文献
997.
Palwinder Singh Jatinder Kaur Bhawna Yadav Sneha Sudha Komath 《Bioorganic & medicinal chemistry》2010,18(12):4212-4223
To search multi drug resistance modulators, acridones carrying hydroxyl amine substituent at N-10 and COOH/Cl at C-4 were investigated for their interactions with the three components of efflux pump viz. P-gp, ATP, and Mg2+. Experimental and theoretical results indicated that the compounds with COOH group at C-4 interact with P-gp and Mg2+ while other set of compounds with Cl at C-4 interact with ATP and Mg2+. Spot assay and R6G influx/efflux assay of compound 3 using Candida albicans showed decrease in the fungal growth and efflux of R6G, respectively, in presence of compound 3 suggesting the suitability of this compound for MDR modulation. 相似文献
998.
Chun Hei Antonio Cheung Xueying Sun Jagat R Kanwar Ji-Zhong Bai LiTing Cheng Geoffrey W Krissansen 《Cancer cell international》2010,10(1):1-11
Background
Survivin is a member of the inhibitor-of-apoptosis (IAP) family which is widely expressed by many different cancers. Overexpression of survivin is associated with drug resistance in cancer cells, and reduced patient survival after chemotherapy and radiotherapy. Agents that antagonize the function of survivin hold promise for treating many forms of cancer. The purpose of this study was to investigate whether a cell-permeable dominant-negative survivin protein would demonstrate bioactivity against prostate and cervical cancer cells grown in three dimensional culture.Results
A dominant-negative survivin (C84A) protein fused to the cell penetrating peptide poly-arginine (R9) was expressed in E. coli and purified by affinity chromatography. Western blot analysis revealed that dNSurR9-C84A penetrated into 3D-cultured HeLa and DU145 cancer cells, and a cell viability assay revealed it induced cancer cell death. It increased the activities of caspase-9 and caspase-3, and rendered DU145 cells sensitive to TNF-α via by a mechanism involving activation of caspase-8.Conclusions
The results demonstrate that antagonism of survivin function triggers the apoptosis of prostate and cervical cancer cells grown in 3D culture. It renders cancer cells sensitive to the proapoptotic affects of TNF-α, suggesting that survivin blocks the extrinsic pathway of apoptosis. Combination of the biologically active dNSurR9-C84A protein or other survivin antagonists with TNF-α therapy warrants consideration as an approach to cancer therapy. 相似文献999.
Bidyut Pal Sanjay Gupta Andrew M.R. New Martin Browne 《Journal of biomechanics》2010,43(10):1923-1930
Understanding the load transfer within a resurfaced femur is necessary to determine the influence of mechanical factors on potential failure mechanisms such as early femoral neck fractures and stress shielding. In this study, an attempt has been made to measure the stem-bone micromotion and implant cup-bone relative displacements (along medial-lateral and anterior-posterior direction), in addition to surface strains at different locations and orientations on the proximal femur and to compare these measurements with those predicted by equivalent FE models. The loading and the support conditions of the experiment were closely replicated in the FE models. A new experimental set-up has been developed, with specially designed fixtures and load application mechanism, which can effectively impose bending and deflection of the tested femurs, almost in any direction. High correlation coefficient (0.92–0.95), low standard error of the estimate (170–379 με) and low percentage error in regression slope (12.8–17.5%), suggested good agreement between the numerical and measured strains. The effect of strain shielding was observed in two (out of eight) strain gauges located on the posterior side. A pronounced strain increase occurred in strain gauges located on the anterior head and neck regions after implantation. Experimentally measured stem-bone micromotion and implant cup-bone relative displacements (0–13.7 μm) were small and similar in trends predicted by the FE models (0–25 μm). Despite quantitative deviations in the measured and numerical results, it appears that the FE model can be used as a valid predictor of the actual strain and stem-bone micromotion. 相似文献
1000.
Ana Maria S. Sim?o Manisha C. Yadav Sonoko Narisawa Mayte Bolean Joao Martins Pizauro Marc F. Hoylaerts Pietro Ciancaglini José Luis Millán 《The Journal of biological chemistry》2010,285(10):7598-7609
We have established a proteoliposome system as an osteoblast-derived matrix vesicle (MV) biomimetic to facilitate the study of the interplay of tissue-nonspecific alkaline phosphatase (TNAP) and NPP1 (nucleotide pyrophosphatase/phosphodiesterase-1) during catalysis of biomineralization substrates. First, we studied the incorporation of TNAP into liposomes of various lipid compositions (i.e. in pure dipalmitoyl phosphatidylcholine (DPPC), DPPC/dipalmitoyl phosphatidylserine (9:1 and 8:2), and DPPC/dioctadecyl-dimethylammonium bromide (9:1 and 8:2) mixtures. TNAP reconstitution proved virtually complete in DPPC liposomes. Next, proteoliposomes containing either recombinant TNAP, recombinant NPP1, or both together were reconstituted in DPPC, and the hydrolysis of ATP, ADP, AMP, pyridoxal-5′-phosphate (PLP), p-nitrophenyl phosphate, p-nitrophenylthymidine 5′-monophosphate, and PPi by these proteoliposomes was studied at physiological pH. p-Nitrophenylthymidine 5′-monophosphate and PLP were exclusively hydrolyzed by NPP1-containing and TNAP-containing proteoliposomes, respectively. In contrast, ATP, ADP, AMP, PLP, p-nitrophenyl phosphate, and PPi were hydrolyzed by TNAP-, NPP1-, and TNAP plus NPP1-containing proteoliposomes. NPP1 plus TNAP additively hydrolyzed ATP, but TNAP appeared more active in AMP formation than NPP1. Hydrolysis of PPi by TNAP-, and TNAP plus NPP1-containing proteoliposomes occurred with catalytic efficiencies and mild cooperativity, effects comparable with those manifested by murine osteoblast-derived MVs. The reconstitution of TNAP and NPP1 into proteoliposome membranes generates a phospholipid microenvironment that allows the kinetic study of phosphosubstrate catabolism in a manner that recapitulates the native MV microenvironment. 相似文献