Preliminary clinical practice in implantation of foldable capsular vitreous body / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To evaluate the effects of foldable capsular vitreous body (FCVB) implantation on the treatment of severe ocular trauma and late silicone oil-dependent eyes due to severe ocular trauma and recurrent retinal detachment. · METHODS: We retrospectively reviewed the four patients (four eyes) with FCVB implantation at our hospital since November 2017. Out of these 4 patients,2 were males and 2 were females, with an average age of 31.5 years and an average intraocular pressure (IOP) of 5.6mmHg pre-operatively. Among those 4 eyes,3 eyes underwent silicone oil tamponade due to severe ocular trauma and the other one was recurrent retinal detachment in silicone oil - filled eye. Standard pars plana vitrectomy (PPV) was performed, and the FCVB was triple folded and implanted in the vitreous cavity of four eyes. The retinal was assessed, as well as visual acuity,IOP, FCVB condition before and after treatment, and applied therapy. ·RESULTS: All of those 4 eyes underwent successfully implantation of FCVB, which remained its proper position. During 1-3mo follow-up, the mean visual acuity was no different compared with pre - operative values.

A review of ANO1-based calcium activated chloride channel modulators / 药学学报

Calcium-activated chloride channel (CaCC) is an anion channel, widely distributed in the human body, taking a part in cell functions including secretion, heart muscle repolarization, nerve signal transmission and several physiological activities. The anoctamin 1 (ANO1) protein is the molecular basis of CaCC and the modification of ANO1 protein will produce a variety of pharmacological effects, such as analgesia, treating dysentery and asthma, even tumor proliferation and migration inhibition. In the past decade, many methods in screening of ANO1 regulators have been developed. Although a series of the ANO1-based CaCC regulatory molecules have been identified, the pharmacological effects of these molecules are not consistent. In this review, we introduce ANO1 protein regulators from many aspects including bio-test methods, structure-activity relationships, and the potential applications.

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.

Synthesis and analgesic activities of phenyl piperazinyl aralkyl ketone derivatives / 药学学报

To explore novel non-opioid analgesic agents, 16 compounds were synthesized and their structures were confirmed by 1H NMR and HR-MS. YX0611-1 was treated as the leading compound. The results of mice writhing model and hot plate model showed that compounds 2, 7, 8, 9, 11 and 15 had obvious analgesic activities in vivo. The test of affinity to mu, delta, kappa receptor displayed that active compounds didn't act on opioid receptor. The results of preliminary toxicity and pharmacokinetic tests showed that compound 7 had better safety and pharmacokinetic properties than that of YX0611-1, and it deserved further development.

Design, synthesis and antalgic activities of aralkyl-ketone-4-piperidol derivatives / 药学学报

A series of aralkyl-ketone-4-piperidol derivatives were synthesized and tested for their analgesic activities. All of the novel 30 compounds were prepared from 4-piperidone and alpha-halo-aralkyl-ketone through five steps, including Boc protection, nucleophilic addition in presence of CeCl3/NaI catalyst, deprotection, condensation and salification. Their structures were confirmed by 1H NMR and HRMS. Preliminary in vivo pharmacological trials showed that most of the synthesized compounds revealed analgesic effects. Among the tested compounds, 8, 13 and 22 exhibited potent analgesic activities in both mice writhing and mice hot plate model. The three compounds have low affinity for mu, delta, kappa receptors, which is a chance to find a better precursor of non-opioid analgesic for further optimization.