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1.
Kopustinskiene DM Jovaisiene J Liobikas J Toleikis A 《Journal of bioenergetics and biomembranes》2002,34(1):49-53
We investigated the effects of KATP channel openers diazoxide and pinacidil on the respiration rate and membrane potential () of rat heart mitochondria, oxidizing pyruvate and malate. Diazoxide and pinacidil (58.8–1348.3 M) increased the V
2 (-ADP) respiration rate accordingly by 13–208% and 30–273% and decreased the by 2–17% and 6–55%. These effects were also similar in the respiration medium without K+. Moreover, carboxyatractyloside completely abolished diazoxide- and pinacidil-induced uncoupling, indicating a role for the mitochondrial adenine nucleotide translocase in this process. 相似文献
2.
Boy KM Guernon JM Shi J Toyn JH Meredith JE Barten DM Burton CR Albright CF Marcinkeviciene J Good AC Tebben AJ Muckelbauer JK Camac DM Lentz KA Bronson JJ Olson RE Macor JE Thompson LA 《Bioorganic & medicinal chemistry letters》2011,21(22):6916-6924
The synthesis, evaluation, and structure-activity relationships of a class of γ-lactam 1,3-diaminopropan-2-ol transition-state isostere inhibitors of BACE are discussed. Two strategies for optimizing lead compound 1a are presented. Reducing the overall size of the inhibitors resulted in the identification of γ-lactam 1i, whereas the introduction of conformational constraint on the prime-side of the inhibitor generated compounds such as the 3-hydroxypyrrolidine inhibitor 28n. The full in vivo profile of 1i in rats and 28n in Tg 2576 mice is presented. 相似文献
3.
Emmanuel Ngeufa Happi Alain Tadjong Tcho Jovita Chi Sirri Jean Duplex Wansi Beate Neumann Hans-Georg Stammler Jean Wandji Norbert Sewald 《Phytochemistry letters》2012,5(3):423-426
Two new tirucallane triterpenoids, 21-methoxy-21,23-epoxy-tirucalla-7,24-dien-3α-ol (1) and 21-methoxy-21,23-epoxy-tirucalla-7,24-diene-1α,3α-diol (2), together with thirteen known compounds were isolated from the CH2Cl2 extract of the stem bark of Araliopsis synopsis. The structures of the compounds were determined by comprehensive analyses of their 1D and 2D NMR, mass spectral (EI and ESI) data and comparison with previously known analogs. Compounds 1–10 were tested against bacteria, fungi and plant pathogen oomycetes by the paper disk agar diffusion assay resulting in missing to low activities corresponding with MICs > 1 mg/mL. However, compounds 5–10 exhibited high cytotoxic activity against the human Caucasian prostate adenocarcinoma cell PC-3 line, with IC50 8.5–12.5 μM compared to the standard Doxorubicin with IC50 = 0.9 μM, while compounds 1, 3 and 4 showed low activity. 相似文献
4.
D.?Styra A.?Usovaite J.?DamauskaiteEmail author A.?Juozulynas 《International journal of biometeorology》2009,53(6):471-477
The prognostic relationship between a decrease of hard cosmic ray flux (HCRF) and subsequent leaps in cardiovascular disease
(CVD) occurrence within 1–3 days is well known. The influence of meteorological situations on human health is also known.
However, no correlation was found between a simultaneous decrease of HCRF and atmospheric pressure and the leaps of CVD on
some days. For the analysis of a prognostic connection between these parameters, empirical criteria have been put forward.
To achieve effective results from analysis, the criteria of a continuous decrease of HCRF to 200 impulses or more within 4 h
and of atmospheric pressure by 2 mmHg or more were used. CVD leaps were considered real when their number increased by 10%
or more in comparison with the average monthly value. The highest prognostic correlation between HCRF decrease and CVD leaps
within 1–2 days was from 64 to 76%. The correlation within 2–3 days was lower. The correlation between atmospheric pressure
decrease and leaps of CVD in 1–2 days and on the same day was 25–44%. It means that, while studying the meteorological effects
on human organisms, other parameters such as temperature, humidity, wind velocity, etc. should also be taken into account.
An essential role in reducing the prognostic accuracy of CVD leaps by a decrease of HCRF relates to the human factor. 相似文献
5.
Three novel derivatives of azobenzene substituted amino acids have been synthesized. The compounds may serve as photoswitchable building blocks in the synthesis of bicyclic peptides or peptide strands interconnected with a photoisomerizable group. 相似文献
6.
Glioblastoma multiforme (GBM) is a highly advanced and invasive brain tumor due to which current treatments cannot completely treat GBM or prevent recurrence. Therefore, adjunctive treatments are required. As part of the invasive and angiogenic nature of GBM, it has been well established that matrix metalloprotease-2 (MMP-2) and MMP-9 are overactive. To better treat GBM using chemotherapy, we have designed a hydrogel-based delivery system that can control the release of drugs based on the activity of MMPs. A model chemotherapeutic agent, cisplatin (CDDP), complexed to an MMP substrate (peptide-linker) was incorporated into poly(ethylene glycol) diacrylate hydrogel wafers having different poly(ethylene glycol) chain lengths (M(n) approximately 574 and 4000). Hydrogel wafers were studied for physical characteristics and drug release in the presence and absence of MMPs. There was a substantial increase in CDDP release for the poly(ethylene glycol) 4000 hydrogel indicating that this chain length provides a mesh size that is sufficient to permit MMP activity within the hydrogel. CDDP bioactivity increased when the cell media was spiked with MMPs (0% cell survival) in case of the longer chain length as compared to in the absence of MMPs (approximately 50% cell survival). The results suggest that this system can be used for selective, local delivery of drugs where higher amounts of the drug are released in response to metastasis, angiogenesis, and invasion-promoting proteases. This strategy may prove to be a novel and effective method to overcome inadequacies in current controlled drug release systems. 相似文献
7.
Guohua Zhao Chet Kwon Aiying Wang James G. Robertson Jovita Marcinkeviciene Rex A. Parker Mark S. Kirby Lawrence G. Hamann 《Bioorganic & medicinal chemistry letters》2013,23(6):1622-1625
Synthesis and structure–activity relationship of a series of substituted piperidinyl glycine 2-cyano-4,5-methano pyrroline DPP-IV inhibitors are described. Improvement of the inhibitory activity and chemical stability of this series of compounds was respectively achieved by the introduction of bulky groups at the 4-position and 1-position of the piperidinyl glycine, leading to a series of potent and stable DPP-IV inhibitors. 相似文献
8.
Simpkins LM Bolton S Pi Z Sutton JC Kwon C Zhao G Magnin DR Augeri DJ Gungor T Rotella DP Sun Z Liu Y Slusarchyk WS Marcinkeviciene J Robertson JG Wang A Robl JA Atwal KS Zahler RL Parker RA Kirby MS Hamann LG 《Bioorganic & medicinal chemistry letters》2007,17(23):6476-6480
The synthesis and structure-activity relationships of novel dipeptidyl peptidase IV inhibitors replacing the classical cyanopyrrolidine P1 group with other small nitrogen heterocycles are described. A unique potency enhancement was achieved with beta-branched natural and unnatural amino acids, particularly adamantylglycines, linked to a (2S,3R)-2,3-methanopyrrolidine based scaffold. 相似文献
9.
To utilize biologic mechanisms to elicit controlled release in response to disease, protease-sensitive devices have been created. Hydrogels were created with pendant peptide-drug complexes. For the matrix metalloproteases (MMPs) examined, a length of six amino acids greatly improved the specificity of the peptide (k(cat)/K(m) approximately 2.4+/-0.1x10(4)M(-1)s(-1)) over shorter sequences (k(cat)/K(m) approximately 4.4+/-0.2x10(2)M(-1)s(-1)). The peptides did not exhibit anti-proliferative effects upon cancer cells, and peptide-platinum complexes showed similar anti-proliferative effects upon the cancer cells compared to the free platinum drugs. Once the peptide-drug complex was incorporated into the hydrogels, the release was dependent upon the presence of MMP in the solution with approximately 35% of platinum released from hydrogels in the presence of MMP and only 10% without MMP in the week examined. The released drug exhibited the expected anti-proliferative activity over several days of incubation. The MMP selective drug delivery holds much potential for treatment of cancer and other diseases. 相似文献
10.
NADH Dehydrogenase Defects Confer Isoniazid Resistance and Conditional Lethality in Mycobacterium smegmatis 总被引:4,自引:0,他引:4 下载免费PDF全文
Lynn Miesel Torin R. Weisbrod Jovita A. Marcinkeviciene Robert Bittman William R. Jacobs Jr. 《Journal of bacteriology》1998,180(9):2459-2467
Isoniazid (INH) is a highly effective drug used in the treatment and prophylaxis of Mycobacterium tuberculosis infections. Resistance to INH in clinical isolates has been correlated with mutations in the inhA, katG, and ahpC genes. In this report, we describe a new mechanism for INH resistance in Mycobacterium smegmatis. Mutations that reduce NADH dehydrogenase activity (Ndh; type II) cause multiple phenotypes, including (i) coresistance to INH and a related drug, ethionamide; (ii) thermosensitive lethality; and (iii) auxotrophy. These phenotypes are corrected by expression of one of two enzymes: NADH dehydrogenase and the NADH-dependent malate dehydrogenase of the M. tuberculosis complex. The genetic data presented here indicate that defects in NADH oxidation cause all of the mutant traits and that an increase in the NADH/NAD+ ratio confers INH resistance. 相似文献