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51.
Dual Inhibition of Human Rhinovirus 2A and 3C Proteases by Homophthalimides 总被引:3,自引:2,他引:3 下载免费PDF全文
Q. May Wang Robert B. Johnson Louis N. Jungheim Jeffrey D. Cohen Elcira C. Villarreal 《Antimicrobial agents and chemotherapy》1998,42(4):916-920
The 2A and 3C proteases encoded by human rhinoviruses (HRVs) are attractive targets for antiviral drug development due to their important roles in viral replication. Homophthalimides were originally identified as inhibitors of rhinovirus 3C protease through our screening effort. Previous studies have indicated that the antiviral activity of certain homophthalimides exceeded their in vitro inhibitory activity against the viral 3C protease, suggesting that an additional mechanism might be involved. Reported here is the identification of homophthalimides as potent inhibitors for another rhinovirus protease, designated 2A. Several homophthalimides exhibit time-dependent inhibition of the 2A protease in the low-micromolar range, and enzyme-inhibitor complexes were identified by mass spectrometry. Compound LY343814, one of the most potent inhibitors against HRV14 2A protease, had an antiviral 50% inhibitory concentration of 4.2 μM in the cell-based assay. Our data reveal that homophthalimides are not only 3C but also 2A protease inhibitors in vitro, implying that the antiviral activity associated with these compounds might result from inactivation of both 2A and 3C proteases in vivo. Since the processing of the viral polyprotein is hierarchical, dual inhibition of the two enzymes may result in cooperative inhibition of viral replication. On the basis of the current understanding of their enzyme inhibitory mechanism, homophthalimides, as a group of novel nonpeptidic antirhinovirus agents, merit further structure-action relationship studies. 相似文献
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D. N. Velázquez Martínez M. Valencia Flores M. López Cabrera J. E. Villarreal 《Psychopharmacology》1995,117(1):91-101
Indorenate (TR3369, 5-methoxytryptamine b-methylcarboxylate HCl) is a 5-HT1-like receptor agonist with hypotensive activity. Here, we describe that indorenate also decreases food intake (ED50 26.1 mg/kg) without an appreciable effect in water intake (the estimated ED50 for water was 589.8 mg/kg). The anorectic activity of indorenate was compared to the effects of amphetamine and other serotonin agonists; the effect of indorenate was smaller than those of the other compounds; however, the effect of indorenate was specific to food, whereas all the other drugs also produced significant decrements in water intake. The serotonin antagonists cinanserin, cyproheptadine, methergoline and methysergide effectively prevented the decrease in food intake produced by indorenate and fenfluramine. Haloperidol, a dopaminergic antagonist, was ineffective in preventing the effect of indorenate although it prevented the anorectic effect of amphetamine. The present results suggest the participation of serotoninergic, but not dopaminergic mechanisms, in the decrease in food intake produced by indorenate. 相似文献
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Michael O. Griffin Guillermo Ceballos Francisco J. Villarreal 《Pharmacological research》2011,63(2):102-107
Tetracyclines were developed as a result of the screening of soil samples for antibiotics. The firstt of these compounds, chlortetracycline, was introduced in 1947. Tetracyclines were found to be highly effective against various pathogens including rickettsiae, as well as both gram-positive and gram-negative bacteria, thus becoming the first class of broad-spectrum antibiotics. Many other interesting properties, unrelated to their antibiotic activity, have been identified for tetracyclines which have led to widely divergent experimental and clinical uses. For example, tetracyclines are also an effective anti-malarial drug. Minocycline, which can readily cross cell membranes, is known to be a potent anti-apoptotic agent. Another tetracycline, doxycycline is known to exert anti-protease activities. Doxycycline can inhibit matrix metalloproteinases which contribute to tissue destruction activities in diseases such as periodontitis. A large body of literature has provided additional evidence for the “beneficial” actions of tetracyclines, including their ability to act as reactive oxygen species scavengers and anti-inflammatory agents. This review provides a summary of tetracycline's multiple mechanisms of action as a means to understand their beneficial effects. 相似文献
54.
A pancreas specificity results from the combination of polyomavirus and Moloney murine leukemia virus enhancer. 总被引:14,自引:1,他引:13 下载免费PDF全文
R Rochford B A Campbell L P Villarreal 《Proceedings of the National Academy of Sciences of the United States of America》1987,84(2):449-453
An infectious recombinant polyomavirus was constructed in which a regulatory region of its genome, the B enhancer region (nucleotides 5128-5265) has been replaced with the 72- or 73-base-pair repeat enhancer from the Moloney murine leukemia virus genome. We show that this recombinant polyomavirus displays a strong tissue specificity for the pancreas of mice. This organ was not permissive for either the parental polyomavirus, which is predominantly kidney and salivary gland specific, or the Moloney murine leukemia virus, which is lymphotropic. This result indicated that tissue specificity can be achieved by a combination of apparently modular elements. Some of the implications of a modular mechanism of tissue specificity are considered. 相似文献
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Brian K Irons Kathleen A Snella Kenneth McCall Eric J MacLaughlin Maumi Villarreal 《American journal of health-system pharmacy》2002,59(17):1615-1625
The third edition of guidelines from the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III [ATP III]) is discussed. The most recent classifications for low-density-lipoprotein (LDL) cholesterol, high-density-lipoprotein (HDL), total cholesterol, and triglycerides are provided. LDL cholesterol goals, cardiovascular risk assessment, therapeutic goals, and pharmacologic treatment options are discussed for both primary and secondary prevention of cardiovascular disease. In addition, the management of dyslipidemia in patients with diabetes and metobolic syndrome is addressed, and the differences between the old and new guidelines are highlighted. The ATP III guidelines may help health care professionals to better screen and categorize patients on the basis of their coronary heart disease (CHD) risk. The updated guidelines recommend more intensive lipid-lowering treatments for primary prevention in patients with two or more risk factors. 相似文献
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58.
CI-750, A novel antidiarrheal agent 总被引:1,自引:0,他引:1
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60.
Portillo Daniel J. Gonzalez Jose Villarreal Carorina Salazar Sophia J. Fasci Anjelyka Wearden Brandt Oseghale Jessica Khalil Anis Perillo Thomas Muenchow Leslie De Lorenzo Robert Hood R. Lyle 《Annals of biomedical engineering》2022,50(8):978-990
Annals of Biomedical Engineering - Oxygenated machine perfusion of human organs has been shown to improve both preservation quality and time duration when compared to the current gold standard:... 相似文献