Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation.
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PMID:BAY 41-2272 activates host defence against local and disseminated Candida albicans infections. 2574 66

In the present study, we describe the synthesis of a novel set of pyridine/pyridinium-type fullerene derivatives. The products were assessed for human immunodeficiency virus-reverse transcriptase inhibition activities. All novel fullerene derivatives showed potent human immunodeficiency virus-reverse transcriptase inhibition without cytotoxicity.
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PMID:The human immunodeficiency virus-reverse transcriptase inhibition activity of novel pyridine/pyridinium-type fullerene derivatives. 2608 Dec 90

Human immunodeficiency virus (HIV-1) reverse transcriptase is a major target for designing anti-HIV drugs. Developed inhibitors are divided into non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs) and nucleoside analog reverse-transcriptase inhibitors (NRTIs) depending on their mechanism. Given that many inhibitors have been studied and for many of them binding affinity constants have been calculated, it is beneficial to analyze the chemical landscape of these families of inhibitors and correlate these inhibition constants with molecular structure descriptors. For this, the HIV-1 RT data was retrieved from the ChEMBL database, carefully curated, and original literature verified, grouped into NRTIs and NNRTIs, analyzed using a hierarchical scaffold classification method and modelled with best multi-linear regression approach. Analysis of the HIV-1 NNRTIs subset results in ten different common structural parent types of oxazepanone, piperazinone, pyrazine, oxazinanone, diazinanone, pyridine, pyrrole, diazepanone, thiazole, and triazine. The same analysis for HIV-1 NRTIs groups structures into four different parent types of uracil, pyrimide, pyrimidione, and imidazole. Each scaffold tree corresponding to the parent types has been carefully analyzed and examined, and changes in chemical structure favorable to potency and stability are highlighted. For both subsets, descriptive and predictive QSAR models are derived, discussed and externally validated, revealing general trends in relationships between molecular structure and binding affinity constants in structurally diverse datasets. Data and QSAR models are available at the QsarDB repository (http://dx.doi.org/10.15152/QDB.202).
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PMID:Chemical structure and correlation analysis of HIV-1 NNRT and NRT inhibitors and database-curated, published inhibition constants with chemical structure in diverse datasets. 2873 70


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