Sulfonilamidothiopyrimidone and thiopyrimidone derivatives as selective COX-2 inhibitors: synthesis, biological evaluation, and docking studies.

Newly synthesized sulfonilamidothiopyrimidone derivatives and a subset of 14 sulfonilamidothiopyrimidones and thiopyrimidones selected by an MTT assays cell viability guided selection from an in house collection were evaluated to determine the inhibitory effect on the PGE(2) formation in human peripheral blood lymphocytes (PBLs) using commercial ELISA. The newly synthesized sulfonilamidothiopyrimidone derivatives showed interesting pharmacological activities. Preliminary in vitro assays showed that compounds 2-5 are endowed with very high activity.

TNF-α contributes to caspase-3 independent apoptosis in neuroblastoma cells: role of NFAT.

There is increasing evidence that soluble factors in inflammatory central nervous system diseases not only regulate the inflammatory process but also directly influence electrophysiological membrane properties of neurons and astrocytes. In this context, the cytokine TNF-α (tumor necrosis factor-α) has complex injury promoting, as well as protective, effects on neuronal viability. Up-regulated TNF-α expression has also been found in various neurodegenerative diseases such as cerebral malaria, AIDS dementia, Alzheimer's disease, multiple sclerosis, and stroke, suggesting a potential pathogenic role of TNF-α in these diseases as well.

Acetaminophen induces apoptosis in rat cortical neurons.

Background: Acetaminophen (AAP) is widely prescribed for treatment of mild pain and fever in western countries. It is generally considered a safe drug and the most frequently reported adverse effect associated with acetaminophen is hepatotoxicity, which generally occurs after acute overdose. During AAP overdose, encephalopathy might develop and contribute to morbidity and mortality.

Amyloid-β induces cyclooxygenase-2 and PGE2 release in human astrocytes in NF-κ B dependent manner.

Both amyloid-β peptide 1-42 (Aβ1-42) formation and cyclooxygenase-2 (COX-2) have been involved in the pathogenesis of Alzheimer's disease (AD), a devastating neurological disorder. However, the relationship between Aβ1-42 and COX-2 is unclear. We found that the addition of Aβ1-42 to astrocytoma cultures induced COX-2 mRNA and protein and PGE2 synthesis in primary human astrocytes and in human astrocytoma cell lines.

Nuclear factor-kappaB activation regulates cyclooxygenase-2 induction in human astrocytes in response to CXCL12: role in neuronal toxicity.

Neurodegenerative and neuroinflammatory disorders are commonly associated with local chemokine release. In other way, emerging data indicate that the prostaglandin E2 (PGE(2)), one of the major prostaglandins produced in the brain, play a central role in several pathological diseases. In this study, we investigated the relationship between CXCL12, cyclooxygenase (COX)-2 and PGE(2) in human brain cells.

HIV-2 induces NF-kappaB activation and cyclooxygenase-2 expression in human astroglial cells.

HIV-2 invades CNS and causes neurological disease as well as HIV-1 does. Induction of COX-2 in CNS of HIV-1 infected people has been proposed as a cause of cognitive impairment, so we tested whether HIV-2 may cause damage by a similar mechanism. COX-2 mRNA and protein expression were induced in human astrocytes upon interaction with HIV-2, being this induction abrogated by CXCR4 antagonists.

Extracellular HIV-Tat induces cyclooxygenase-2 in glial cells through activation of nuclear factor of activated T cells.

Both the HIV-1 protein Tat and cyclooxygenase-2 (COX-2) have been involved in the neuropathogenesis associated with HIV-1 infection. However, the relationship among them has not been addressed. Here, we found that extracellular Tat was able to induce COX-2 mRNA and protein expression and PGE2 synthesis in astrocytoma cell lines and primary human astrocytes.