The structure-activity relationships of novel α7 nicotinic acetylcholine receptor agonists based on indolizine scaffold / 药学学报

Alpha7 nicotinic acetylcholine receptor (α7 nAChR) is a ligand-gated ion channel critical for cognition, learning and memory. Deficiency of neuronal α7 nAChR has been implicated in the cognitive deficits and neuropsychiatric disorders. Chemical activation of α7 nAChR improves neurological functions in animal models. In this study, we designed and synthesized a series of indolizine derivatives with various substitutions at different positions on the scaffold, and investigated their structure-activity relationships (SAR). All compounds were screened and evaluated for their agonist activity using the two-electrode voltage clamp recording system in Xenopus oocytes expressing human α7 nAChR. Compound 16c carrying 6-methylindolizine moiety activates α7 nAChR with EC50 at 1.60±0.19 μmol·L-1 and maximum effect (Emax) of 69.0%±2.8% compared with 3 mmol·L-1 ACh. Compound 17b with 8-cyclopropyl substitution shows an increased Emax of 81.1%±9.3% with EC50 at 2.74±0.74 μmol·L-1. The SAR of the series shows that introducing the small hydrophobic groups at 6- or 8- position can improve both potency and maximum effect.

Relationship between vitamin D deficiency and early-onset neonatal sepsis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the effect of vitamin D level on early-onset sepsis (EOS) in neonates.</p><p><b>METHODS</b>Seventy-eight full-term neonates with EOS were used as the research group (EOS group). sixty healthy full-term neonates without clinical and/or laboratory features related to infections were used as the control group. Blood samples of the neonates and their mothers in both groups were collected within 72 hours of delivery to determine 25-hydroxyvitamin D(25-OHD) levels. The rate of vitamin D deficiency in the neonates and the level of 25-OHD supplemented to their mothers during pregnancy were compared between the two groups.</p><p><b>RESULTS</b>There was a significant positive correlation between the serum level of 25-OHD of the mothers and that of the neonates in both groups (EOS group: r=0.797, P<0.01; control group: r=0.929, P<0.01). The neonates and their mothers in the EOS group had significantly lower 25-OHD levels than those in the control group (P<0.01). The rate of vitamin D deficiency among the neonates in the EOS group was significantly higher than that of the control group (P<0.01). The level of vitamin D supplemented to the mothers during the last 3 months of pregnancy in the EOS group was significantly lower than that in the control group (P<0.01).</p><p><b>CONCLUSIONS</b>Low serum level of 25-OHD is associated with the development of early-onset sepsis in full-term neonates.</p>