Design, synthesis, and structure-activity relationship studies of 6-benzo[]indeno[1,2-]thiophen-6-one derivatives as DYRK1A/CLK1/CLK4/haspin inhibitors.

A series of sulfur-containing tetracycles was designed and evaluated for their ability to inhibit protein kinase DYRK1A, a target known to have several potential therapeutic applications including cancers, Down syndrome or Alzheimer's disease. Our medicinal chemistry strategy relied on the design of new compounds using ring contraction/isosteric replacement and constrained analogy of known DYRK1A inhibitors, thus resulting in their DYRK1A inhibitory activity enhancement. Whereas a good inhibitory effect of targeted DYRK1A protein was observed for 5-hydroxy compounds 4i-k (IC = 35-116 nM) and the 5-methoxy derivative 4e (IC = 52 nM), a fairly good selectivity towards its known DYRK1B off-target was observed for 4k.

Long-term tracking of social structure in groups of rats.

Rodents serve as an important model for examining both individual and collective behavior. Dominance within rodent social structures can determine access to critical resources, such as food and mating opportunities. Yet, many aspects of the intricate interplay between individual behaviors and the resulting group social hierarchy, especially its evolution over time, remain unexplored.

Influence of titanium and titanium-zirconium alloy as implant materials on implant stability of maxillary implant retained overdenture: a randomized clinical trial.

Background: Long-term success of implant restoration depends on many factors one of them is the sufficient implant stability which is lowered in compromised bone density sites such as the maxilla as it is categorized as type III & IV bone, so searching for a new innovation and updates in implant material and features is very mandatory. So, the aim of this study was to compare between two implant materials (roxolid and traditional titanium) on the primary and secondary stability of implant retained maxillary overdenture.

Methods: Eighteen completely edentulous patients were selected.

Development of 5-hydroxybenzothiophene derivatives as multi-kinase inhibitors with potential anti-cancer activity.

Chemoresistance in cancer challenges the classical therapeutic strategy of 'one molecule-one target'. To combat this, multi-target therapies that inhibit various cancer-relevant targets simultaneously are proposed. We introduce 5-hydroxybenzothiophene derivatives as effective multi-target kinase inhibitors, showing notable growth inhibitory activity across different cancer cell lines.