Synthesis and structure-activity relationships of constrained heterocyclic analogues of combretastatin A4

A series of combretastatin A4 (CA4) analogues with a lactam or lactone ring fused to the trimethoxyphenyl or the B‐phenyl moiety were synthesized in an efficient and stereoselective manner by using a domino Heck–Suzuki–Miyaura coupling reaction. The vascular‐disrupting potential of these conformationally restricted CA4 analogues was assessed by various in vitro assays: inhibition of tubulin polymerization, modification of endothelial cell morphology, and disruption of endothelial cell cords. Compounds were also evaluated for their growth inhibitory effects against murine and human tumor cells. B‐ring‐constrained derivatives that contain an oxindole ring (in contrast to compounds with a benzofuranone ring) as well as analogues bearing a six‐membered lactone core fused to the trimethoxyphenyl ring are endowed with significant biological activity. The most potent compound of this series (oxindole 9 b ) is of particular interest, as it combines chemical stability and a biological activity profile characteristic of a vascular‐disrupting agent.     

Drivers for retrofit: a sociocultural approach to houses and inhabitants

ABSTRACT

Private households constitute approximately 30% of the total energy consumption in Denmark. The greatest potential for reducing energy consumption in private households is through retrofits of existing houses. One of the most common ways to promote retrofits is the act of sending an energy advisor to visit homeowners in order to explain the technological and economic advantages that arise from undertaking a retrofit. However, little is known about how homeowners make sense of retrofits. Based on an extensive anthropological fieldwork study of 12 Danish homeowners who had received energy advice, retrofits were investigated from the perspective of the everyday life of homeowners. Three social dimensions that played an important role when the people in the study discussed house renovation were identified and discussed: houses as part of homeowners’ life cycles and personal events; houses as frameworks for social relations; and houses as markers of social values and status. These results indicate a need to develop new strategies to promote retrofits more effectively, which focus less on the techno-economic aspects and more on the social dimensions.     

脑干蓝斑到前庭神经核的神经环路投射及在压力应激下的激活研究

前庭神经核(Vestibular Nuclei)是保持平衡的关键核团,其功能异常与晕动病、前庭偏头痛、帕 金森氏病等多种疾病状态密切关联,压力应激往往加重以上疾病的症状并伴随着蓝斑(Locus Coeruleus) 去甲肾上腺素能系统的激活。该研究利用转基因小鼠结合病毒示踪显示从蓝斑到前庭神经核的神经投 射,并利用酪氨酸羟化酶(Tyrosine Hydroxylase)抗体免疫荧光染色确定蓝斑-前庭神经核的投射为去甲 肾上腺素能。结果显示,小鼠在睡眠剥夺压力刺激下蓝斑去甲肾上腺素能神经元被强烈激活,而前庭 神经核神经元激活不明显,提示睡眠剥夺可能通过蓝斑-前庭神经核的去甲肾上腺素能神经调制起作 用。该结果可为继续探究蓝斑-前庭神经核神经环路在压力应激与前庭神经核功能调控之间的重要作用 提供解剖结构学基础。     

Tailoring the Surface Chemistry of PEDOT:PSS to Promote Supported Lipid Bilayer Formation

This communication reports on a versatile and substrate-agnostic method to tune the surface chemistry of conducting polymers with the aim of bridging the chemical mismatch between bioelectronic devices and biological systems. As a proof of concept, the surface of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) is grafted with a short-chain oligoethylene glycol monolayer to favor the formation of cell-derived supported lipid bilayers (SLBs). This method is tuned to optimize the affinity between the supported lipid bilayer and the conducting polymer, leading to significant improvements in bilayer quality and therefore electronic readouts. To validate the impact of surface functionalization on the system's ability to transduce biological phenomena into quantifiable electronic signals, the activity of a virus commonly used as a surrogate for SARS-CoV-2 (mouse hepatitis virus) is monitored with and without surface treatment. The functionalized devices exhibit significant improvements in electronic output, stemming from the improved SLB quality, therefore strengthening the case for the use of such an approach in membrane-on-a-chip systems.     

Rhodium(III)‐Catalyzed Synthesis of Aryl Spirocycles by Aromatic C?H Activation/Intramolecular Heck‐Type Reaction

The rhodium(III)‐catalyzed aromatic C H activation/intramolecular Heck‐type reaction has been studied to synthesize spirocyclic compounds, an important class of molecules in medicinal chemistry and natural product synthesis. This approach was efficient with a variety of substituted N‐methoxybenzamides tethered to different cyclic alkenes having a 5‐, 6‐ or 7‐membered ring. This practical method affords sterically hindered o‐substituted aryl spirocycles that are valuable compounds for further functionalization to access relevant building blocks.