HEPT类HIV-1逆转录酶抑制剂的研究进展

逆转录酶是设计抗艾滋病药物研究的选择性靶酶,从作用机制、构效关系等方面综述HEPT及其类似物作为HIV-1逆转录酶抑制剂的研究进展.     

防治痴呆新药的构效关系研究

阿尔茨海默病、帕金森病和血管性痴呆是严重危害老年人生命健康的多发病。目前临床应用的防治痴呆药物的作用机制主要涉及改善胆碱能神经递质、激动多巴胺(DA)受体、阻滞N-甲基-D门冬氨酸(NMDA)受体和改善脑血管功能等。综述了近年来报道的防治痴呆新药的构效关系研究进展。     

New optimized piperamide analogues with potent in vivo hypotensive properties

We describe herein the structural optimization of new piperamide analogues, designed from two natural prototypes, piperine 1 and piperdardine 2, obtained from Piper tuberculatum Jacq. (Piperaceae). Molecular modeling studies using semiempirical AM1 method were made in order to establish rational modifications to optimize them by molecular simplification. The targeted compounds (10) and (11) were respectively obtained using benzaldehyde (12) and para-anisaldehyde (13) as starting materials. ¹H NMR spectra showed that the target compounds were diastereoselectively obtained as the (E)-isomer, the same geometry of the natural prototypes. These new synthetic amides presented significant hypotensive effects in cardiovascular essays using in vivo methodologies. Compound 11 (N-[5-(4′-methoxyphenyl)-2(E)-pentenoyl]thiomorpholine) showed a potency 10,000 times greater than its prototype 5, evidencing an optimization of the molecular architecture for this class of hypotensive drug candidates.     

Heating pattern of helical microwave intracavitary oesophageal applicator

Helical microwave intracavitary oesophageal (HMIO) applicators were designed to operate at frequencies of 433 MHz and 915 MHz. Heating patterns were studied within muscle-equivalent phantom by thermographic camera and fibreoptic thermometers. The results showed that frequency significantly influenced the microwave heating pattern. The 433 MHz applicator had a single power deposition region, the longitudinal specific absorption rate (SAR) distribution appeared to be nearly even, and the maximum SAR value occurred close to the centre of the active length of the applicator. The 915 MHz applicator had two power deposition regions, the peak SAR values occurred at about 1/4 and 3/4 of the active length respectively, The radial SAR distribution suggested that there is no obvious difference between the 433 MHz and 915 MHz applicators in that the average radial penetration of 50% surface SAR (RP50) was about 0.65 cm. It was also shown that power deposition was axially symmetric for both 433 MHz and 915 MHz HMIO applicators. It is shown that better impedance matching is more important for intracavitary hyperthermia than for external hyperthermia. Choosing HMIO applicators in clinical practice is also discussed.     

Improving therapeutic outcomes in autism spectrum disorders: Enhancing social communication and sensory processing through the use of interactive robots

For children with autism spectrum disorders (ASDs), social robots are increasingly utilized as therapeutic tools in order to enhance social skills and communication. Robots have been shown to generate a number of social and behavioral benefits in children with ASD including heightened engagement, increased attention, and decreased social anxiety. Although social robots appear to be effective social reinforcement tools in assistive therapies, the perceptual mechanism underlying these benefits remains unknown. To date, social robot studies have primarily relied on expertise in fields such as engineering and clinical psychology, with measures of social robot efficacy principally limited to qualitative observational assessments of children's interactions with robots. In this review, we examine a range of socially interactive robots that currently have the most widespread use as well as the utility of these robots and their therapeutic effects. In addition, given that social interactions rely on audiovisual communication, we discuss how enhanced sensory processing and integration of robotic social cues may underlie the perceptual and behavioral benefits that social robots confer. Although overall multisensory processing (including audiovisual integration) is impaired in individuals with ASD, social robot interactions may provide therapeutic benefits by allowing audiovisual social cues to be experienced through a simplified version of a human interaction. By applying systems neuroscience tools to identify, analyze, and extend the multisensory perceptual substrates that may underlie the therapeutic benefits of social robots, future studies have the potential to strengthen the clinical utility of social robots for individuals with ASD.     

A propensity-matched analysis of clinical outcomes between open thyroid lobectomy and high-intensity focused ultrasound (HIFU) ablation of benign thyroid nodules

Background

High-intensity focused ultrasound is a promising, nonoperative treatment for benign thyroid nodules. Our study aimed to compare treatment outcomes of single-session high-intensity focused ultrasound ablation with open lobectomy after propensity score matching.

Modeling of activity landscapes for drug discovery

Introduction: Activity landscapes (ALs) are graphical representations that integrate compound structure and potency relationships. These computer-generated models enable the interactive large-scale analysis of structure–activity relationships (SARs) and complement traditional approaches to study SARs of individual compound series in a qualitative or quantitative manner. A variety of AL designs have been reported.

Areas covered: The concept of activity landscapes is introduced and different methodologies to represent 2D or 3D AL representations of large compound data sets are described on the basis of original literature references. Several AL variants and extensions have been generated for special applications in medicinal chemistry. These include, for example, AL views of evolving data sets with constant topology, selectivity landscapes and multi-target ALs, or molecular mechanism and multi-property maps. Furthermore, the applicability domain of the AL concept is discussed including specific requirements for practical utility in medicinal chemistry opportunities for further developments.

Expert opinion: AL modeling has substantially extended conventional ways to study SARs. The AL concept is inseparable from the notion of activity cliffs that are of high interest in SAR analysis. AL design is an area of active research at the interface between chemoinformatics and medicinal chemistry with potential for further growth. Special emphasis must be put on increasing the usability of AL models for practicing medicinal chemists.