Facile and efficient syntheses of a series of N-benzyl and N-biphenylmethyl substituted imidazole derivatives based on (E)-urocanic acid, as Angiotensin II AT1 receptor blockers

In the present work, a facile and efficient route for the synthesis of a series of N-substituted imidazole derivatives is described. Docking studies have revealed that N-substituted imidazole derivatives based on (E)-urocanic acid may be potential antihypertensive leads. Therefore, new AT1 receptor blockers bearing either the benzyl or the biphenylmethyl moiety at the N-1 or N-3 position, either the (E)-acrylate or the propanoate fragment and their related acids at the C-4 position as well as a halogen atom at the C-5 position of the imidazole ring, were synthesized. The newly synthesized analogues were evaluated for binding to human AT1 receptor. The biological results showed that this class of molecules possesses moderate or no activity, thus not always confirming high docking scores. Nonetheless, important conclusions can be derived for their molecular basis of their mode of action and help medicinal chemists to design and synthesize more potent ones. An aliphatic group as in losartan seems to be important for enhancing binding affinity and activity

Virtualization and cognitive management of real world objects in the internet of things

This paper presents a framework for the virtualization of real world objects and the cognitive management of their virtual counterparts. The framework consists of three levels of functionality and each level comprises cognitive entities that provide the means for self-management and learning, allowing for smart, flexible applications and objects. The presented framework enables the abstraction of the heterogeneity that derives from the vast amount of diverse objects/devices, while enhancing reliability and facilitates the consideration of the views of various users/stakeholders (owners of objects & communication means) for ensuring proper application provision, business integrity and, therefore, maximization of exploitation opportunities. The paper also presents a corresponding prototype that has been developed for the validation of the proposed approach, in a real-life fire detection scenario in a Smart Home

Enabling smart cities through a cognitive management framework for the internet of things

The Internet of Things (IoT) is expected to substantially support sustainable development of future smart cities. This article identifies the main issues that may prevent IoT from playing this crucial role, such as the heterogeneity among connected objects and the unreliable nature of associated services. To solve these issues, a cognitive management framework for IoT is proposed, in which dynamically changing real-world objects are represented in a virtualized environment, and where cognition and proximity are used to select the most relevant objects for the purpose of an application in an intelligent and autonomic way. Part of the framework is instantiated in terms of building blocks and demonstrated through a smart city scenario that horizontally spans several application domains. This preliminary proof of concept reveals the high potential that self-reconfigurable IoT can achieve in the context of smart cities

W254 in furin functions as a molecular gate promoting anti-viral drug binding: Elucidation of putative drug tunneling and docking by non-equilibrium molecular dynamics

Furins are serine endoproteases that process precursor proteins into their biologically active forms, and they play essential roles in normal metabolism and disease presentation, including promoting expression of bacterial virulence factors and viral pathogenesis. Thus, furins represent vital targets for development of antimicrobial and antiviral therapeutics. Recent experimental evidence indicated that dichlorophenyl (DCP)-pyridine “BOS” drugs (e.g., BOS-318) competitively inhibit human furin by an induced-fit mechanism in which tryptophan W254 in the furin catalytic cleft (FCC) functions as a molecular gate, rotating nearly 180o through a steep energy barrier about its chi-1 dihedral to an “open” orientation, exposing a buried (i.e., cryptic) hydrophobic pocket 1. Once exposed, the non-polar DCP group of BOS-318, and similar halo-phenyl groups of analogs, enter the cryptic pocket, stabilizing drug binding. Here, we demonstrate flexible-receptor docking of BOS-318 (and various analogs) was unable to emulate the induced-fit motif, even when tryptophan was replaced with less bulky phenylalanine or glycine. While either substitution allowed access to the hydrophobic pocket for most ligands tested, optimal binding was observed only for W254, inferring a stabilizing effect of the indole sidechain. Furthermore, non-equilibrium steered molecular dynamics (sMD) in which the bound drugs (or their fragments) were extracted from the FCC did not cause closure of the open W254 gate, consistent with the thermodynamic stability of the open or closed W254 orientations. Finally, interactive molecular dynamics (iMD) revealed two putative conduits of drug entry and binding into the FCC, each coupled with W254 dihedral rotation and opening of the cryptic pocket. The iMD simulations further revealed ligand entry and binding in the FCC is likely driven in part by energy fluxes stemming from disruption and re-formation of ligand and protein solvation shells during drug migration from the solution phase into the FCC

A Cognitive Management Framework for Empowering the Internet of Things

This work presents a Cognitive Management framework for empowering the Internet of Things (IoT). This framework has the ability to dynamically adapt its behaviour, through self-management functionality, taking into account information and knowledge (obtained through machine learning) on the situation (e.g., internal status and status of environment), as well as policies (designating objectives, constraints, rules, etc.). Cognitive technologies constitute a unique and efficient approach for addressing the technological heterogeneity of the IoT and obtaining situation awareness, reliability and efficiency. The paper also presents a first indicative implementation of the proposed framework, comprising real sensors and actuators. The preliminary results of this work demonstrate high potential towards self-reconfigurable IoT

A cognitive management framework for empowering the internet of things

This work presents a Cognitive Management framework for empowering the Internet of Things (IoT). This framework has the ability to dynamically adapt its behaviour, through self-management functionality, taking into account information and knowledge (obtained through machine learning) on the situation (e.g., internal status and status of environment), as well as policies (designating objectives, constraints, rules, etc.). Cognitive technologies constitute a unique and efficient approach for addressing the technological heterogeneity of the IoT and obtaining situation awareness, reliability and efficiency. The paper also presents a first indicative implementation of the proposed framework, comprising real sensors and actuators. The preliminary results of this work demonstrate high potential towards self-reconfigurable IoT. © The Author(s)