CXCR4 inhibitors are promising agents for the treatment of cancer metastasis and inflammation. A series of novel tertiary amine derivatives targeting CXCR4 were designed, synthesized, and evaluated. The central benzene ring linker and side chains were modified and optimized to study the structure-activity relationship. Seven compounds displayed much more potent activity than the reference drug, AMD3100, in both the binding affinity assay and the blocking of Matrigel invasion functional assay. These compounds exhibited effective concentration ranging from 1 to 100 nM in the binding affinity assay and inhibited invasion from 65.3% to 100% compared to AMD3100 at 100 nM. Compound IIn showed a 50% suppressive effect against carrageenan-induced paw inflammation in a mouse model, which was as effective as the peptidic antagonist, TN14003 (48%). These data demonstrate that symmetrical bis-tertiary amines are unique CXCR4 inhibitors with high potency.
Nursing homes are required to conduct a comprehensive assessment and screening of residents with urinary incontinence (UI) and indwelling catheter upon admission, and if there is a change in cognition, physical ability, or urinary tract function (Centers for Medicare and Medicaid Services [CMS], 2005). The desired goal is to improve the quality of care through the maintenance and the restoration of bladder function. CMS regulations and revised Tag F315 mandate that long-term care facilities appropriately assess and treat the specific bladder disorder of UI and decrease the inappropriate use of indwelling urinary catheters. Assessment includes evaluation for reversible factors that may cause UI, such as urinary retention and urinary tract infection. The scope of this article is to demonstrate the relationship between these bladder disorders and assessments that can be performed by nursing staff. Because invasive instrumentation of the bladder can increase the likelihood of urinary tract infections, the use of non-invasive technology that ensures quality and evidence-based clinical practice, while preventing associated medical problems in vulnerable residents, is necessary for bladder assessment in the extended care setting. With this technology, assessment of bladder function is easy for staff and provides information that can be vital to successful nursing care outcomes. The staff of CRISTA Senior Community changed clinical practice through incorporation of technology to determine the presence of bladder dysfunction. Staff accurately and effectively applied ultrasonography to determine the bladder volume and abnormalities with bladder emptying, with ultimate improvement in resident care. Adoption of technology can preserve the resident's dignity and respect, while ensuring the highest level of bladder function.
A series of pyridine derivatives were synthesized as potential inhibitors of chemokine receptor type 4. This chemokine receptor has been linked to various disease pathways including HIV-1 proliferation, autoimmune disorders, inflammatory diseases, and cancer metastasis. The compounds were tested for activity using an affinity binding assay and an assay that tests the ability to inhibit cell invasion. Two hit compounds (2b and 2j) have been identified for further evaluation that inhibit cell invasion by at least 50% and have an effective concentration of less than 100 nM in the binding affinity assay. The structures of the synthesized compounds were confirmed by spectral data.
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