Rational Design of Advanced Triboelectric Materials for Energy Harvesting and Emerging Applications.

The properties of materials play a significant role in triboelectric nanogenerators (TENGs). Advanced triboelectric materials for TENGs have attracted tremendous attention because of their superior advantages (e.g., high specific surface area, high porosity, and customizable macrostructure). These advanced materials can be extensively applied in numerous fields, including energy harvester, wearable electronics, filtration, and self-powered sensors. Hence, designing triboelectric materials as advanced functional materials is important for the development of TENGs. Herein, the structural modification methods based on electrospinning to improve the triboelectric properties and the latest research progress in this kind of TENGs are systematically summarized. Preparation methods and design trends of nanofibers, microspheres, hierarchical structures, and doping nanomaterials are highlighted. The factors influencing the formation and properties of triboelectric materials are considered. Furthermore, the latest progress on the applications of TENGs is systematically elaborated. Finally, the challenges in the development of triboelectric materials are discussed, thereby guiding researchers in the large-scale application of TENGs.

Discovery of Novel Indolealkylpiperazine Derivatives as Potent 5-HT1A Receptor Agonists for the Potential Future Treatment of Depression.

Depression is a severe psychiatric disorder that affects over 100 million people worldwide. 5-HT1A receptor agonists have been implicated in the treatment of a variety of central nervous system diseases, especially depression. In this study, based on FW01, a selective potent 5-HT1AR agonist discovered via dynamic pharmacophore-based virtual screening, a series of indolealkylpiperazine derivatives with a benzamide moiety were designed and synthesized by the modification of the amide tail group as well as indole head group of FW01. Among all tested compounds, 13m displayed potent agonistic activity towards 5-HT1AR with an EC50 value of 1.01 nM. Molecular docking studies were performed to disclose the mechanism of its potent agonistic activity and high selectivity. Finally, the activation model of 5-HT1AR induced by 13m was proposed.

Discovery of aryl-piperidine derivatives as potential antipsychotic agents using molecular hybridization strategy.

Schizophrenia is a chronic, disabling mental disorder that affects about one percent of world's population. Drugs acting on multiple targets have been demonstrated to provide superior efficacy in schizophrenia than agents acting on single target. In this study, based on FW01, a selective potent 5-HT1A receptor agonist discovered via dynamic pharmacophore-based virtual screening, molecular hybridization strategy was employed to optimize its in vitro activity over D2 and 5-HT2A receptors. The optimized compound 9f was found to show dual potent D2 and 5-HT2A receptors antagonistic activity. In addition, compound 9f showed good in vivo metabolic stability with t1/2 of 2 h in ICR mice and good capability to penetrate the blood-brain barrier with Kp value of 4.03. These results demonstrated that the dual D2 and 5-HT1A receptor antagonist 9f could serve as a promising lead compound to discover potent antipsychotic agents.

Design, Synthesis, and Structure-Activity Relationship Studies of Novel Indolyalkylpiperazine Derivatives as Selective 5-HT1A Receptor Agonists.

5-HT1A receptor (5-HT1AR) agonists have been implicated in the treatment of a variety of central nervous system (CNS) diseases such as depression and anxiety, et al. Based on our previously found compound FW01 (Ki = 51 ± 16 nM) obtained by virtual screening, a series of FW01 derivatives were designed and synthesized by the modification of the amide tail group as well as indole headgroup of FW01. SAR exploration found that amide tail group and indole headgroup play pivotal roles in determining the binding affinity and selectivity on dopamine and serotonin receptor subtypes. Among all tested compounds, 9_24 has a Ki value of 5 ± 0.6 nM with a good selectivity toward 5-HT1AR. The [35S] GTPγS assay showed that 9_24 is a full agonist toward 5-HT1AR with an EC50 value of 0.059 nM, which shows 266.2 and 146.4-fold selectivity to 5-HT2A and D3 respectively. Molecular dynamics simulations and molecular docking studies with 5-HT1AR-9_24 were performed to disclose the mechanism of its high activity and selectivity. Finally, a detailed stepwise 9_24 induced signal transduction mechanism of 5-HT1AR is proposed.