Prospecting for a quinoline containing selenium for comorbidities depression and memory impairment induced by restriction stress in mice

Abstract

Rationale Depression is often associated with memory impairment, a clinical feature of Alzheimer’s disease (AD), but no effective treatment is available. 7-Chloro-4-(phenylselanyl) quinoline (4-PSQ) has been studied in experimental models of diseases that affect the central nervous system. Objectives The pharmacological activity of 4-PSQ in depressive-like behavior associated with memory impairment induced by acute restraint stress (ARS) in male Swiss mice was evaluated. Methods ARS is an unavoidable stress model that was applied for a period of 240 min. Ten minutes after ARS, animals were intragastrically treated with canola oil (10 ml/kg) or 4-PSQ (10 mg/kg) or positive controls (paroxetine or donepezil) (10 mg/kg). Then, after 30 min, mice were submitted to behavioral tests. Corticosterone levels were evaluated in plasma and oxidative stress parameters; monoamine oxidase (MAO)-A and MAO -B isoform activity; mRNA expression levels of kappa nuclear factor B (NF-κB); interleukin (IL)-1β, IL-18, and IL-33; phosphatidylinositol-se-kinase (PI3K); protein kinase B (AKT2), as well as acetylcholinesterase activity were evaluated in the prefrontal cortex and hippocampus. Results 4-PSQ attenuated the depressive-like behavior, self-care, and memory impairment caused by ARS. Based on the evidence, we believe that effects of 4-PSQ may be associated, at least in part, with the attenuation of HPA axis activation, attenuation of alterations in the monoaminergic system, modulation of oxidative stress, reestablishment of AChE activity, modulation of the PI3K/AKT2 pathway, and reduction of neuroinflammation. Conclusions These results suggested that 4-PSQ exhibited an antidepressant-like effect and attenuated the memory impairment induced by ARS, and it is a promising molecule to treat these comorbidities.

Selenium in Bodily Homeostasis: Hypothalamus, Hormones, and Highways of Communication

“…Another compound, 7-chloro-4-(phenylsenyl) quinoline (4-PSQ), was also recently shown by de Oliveira and colleagues to be effective in attenuating depressive-like phenotypes in mice following acute restraint stress (ARS) [ 229 ]. Among other mechanisms, the researchers reported that direct attenuation of the HPA axis activation may be involved in this finding, as 4-PSQ treatment prior to ARS maintained circulating corticosterone (CORT), the main active GC in mice, at levels similar to those of the unstressed controls [ 229 ]. This suggested that prophylactic administration of 4-PSQ might have the capacity to prevent hyperactivation of the HPA axis, keeping CORT levels near baseline.…”

Radical cyclization of alkynyl aryl ketones for the synthesis of 3-seleno-substituted thiochromones and chromones

“…Additionally, the synthesis of new molecules containing the selenium atom has attracted great interest in organic synthesis and medicinal chemistry due to the broad and interesting pharmacological properties attributed to these compounds. 10 Reports demonstrate that organoselenium compounds show antidepressant, 11 anticancer, 12 anti-Alzheimer's disease, 13 and antiviral activities. 14 Furthermore, recent studies have shown that the incorporation of selenium into organic molecules, especially in the heterocyclic core, can considerably increase the pharmacological activities of these compounds.…”