Boron-Based Compounds最新文献

Radiolabeling Strategies for Boron Clusters 硼簇的放射性标记策略

Boron-Based Compounds Pub Date : 2018-07-12 DOI: 10.1002/9781119275602.CH2.5

K. Gona, V. Gómez‐Vallejo, Irina Manea, J. Malmquist, J. Koziorowski, J. Llop

引用次数: 0

Carboranes as Hydrophobic Pharmacophores 碳硼烷作为疏水性药效团

Boron-Based Compounds Pub Date : 2018-07-12 DOI: 10.1002/9781119275602.CH1.1

Y. Endo

{"title":"Carboranes as Hydrophobic Pharmacophores","authors":"Y. Endo","doi":"10.1002/9781119275602.CH1.1","DOIUrl":"https://doi.org/10.1002/9781119275602.CH1.1","url":null,"abstract":"A pharmacophore is a partial structure in which important functional groups and hydrophobic structure are arranged in suitable positions for binding to a receptor [1]. Typically, hydrophilic functional groups of the pharmacophore interact with the receptor by hydrogen bonding and/or ionic bonding, and the hydrophobic structure interacts with a hydrophobic surface of the receptor. While hydrogen bonding plays a key role in specific ligand–receptor recognition, the hydrophobic interaction between receptor and drug molecule is especially important in determining the binding affinity. The difference of binding constants between a ligand having a suitable hydrophobic group and a ligand without such a group can be as large as 1000‐fold. In medicinal drug design, the hydrophobic structures are often composed of aromatic and heteroaromatic rings, which also play a role in fixing the arrangement of functional groups appropriately for binding to the receptor. On the other hand, three‐dimensional hydrophobic structures are not yet widely used in drug design, even though they could be well suited for interaction with the three‐dimensional hydrophobic binding pockets of receptors. It is noteworthy that various steroid hormones target distinct steroid hormone receptors owing to differences of functionalization of the hydrophobic steroidal skeleton. The binding of the natural ligand 17β‐estradiol to human estrogen receptor‐α (ERα) is illustrated in Figure 1.1.1 as an example. The large number of steroid hormones may be a consequence of evolutionary diversification of the functions of the steroidal skeleton. In this context, we aimed to establish a new three‐dimensional hydrophobic skeletal structure for medicinal drug design. Carboranes as Hydrophobic Pharmacophores: Applications for Design of Nuclear Receptor Ligands","PeriodicalId":124832,"journal":{"name":"Boron-Based Compounds","volume":"71 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122885124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Cobaltabisdicarbollide-based Synthetic Vesicles 钴二羰基合成囊泡

Boron-Based Compounds Pub Date : 2018-07-12 DOI: 10.1002/9781119275602.CH2.2

Clara Viñas i Teixidor, F. Teixidor, A. Harwood

引用次数: 2

Boron Cluster Modifications with Antiviral, Anticancer, and Modulation of Purinergic Receptors’ Activities Based on Nucleoside Structures 基于核苷结构的硼簇修饰抗病毒、抗癌和嘌呤能受体活性调节

Boron-Based Compounds Pub Date : 2018-07-12 DOI: 10.1002/9781119275602.CH1.2

Anna Adamska‐Bartłomiejczyk, K. Bednarska, Magdalena Białek-Pietras, Z. Kiliańska, Adam Mieczkowski, A. Olejniczak, E. Paradowska, M. Studzińska, Z. Sułowska, J. Żołnierczyk, Z. Leśnikowski

{"title":"Boron Cluster Modifications with Antiviral, Anticancer, and Modulation of Purinergic Receptors’ Activities Based on Nucleoside Structures","authors":"Anna Adamska‐Bartłomiejczyk, K. Bednarska, Magdalena Białek-Pietras, Z. Kiliańska, Adam Mieczkowski, A. Olejniczak, E. Paradowska, M. Studzińska, Z. Sułowska, J. Żołnierczyk, Z. Leśnikowski","doi":"10.1002/9781119275602.CH1.2","DOIUrl":"https://doi.org/10.1002/9781119275602.CH1.2","url":null,"abstract":"Nucleoside analogs have been in clinical use for several decades and have become cornerstones of treatment for patients with cancer or viral infections [1,2]. This is complemented with nucleoside antibiotics, a large family of microbial natural products and synthetic derivatives derived from nucleosides and nucleotides [3]. The approval of several new nucleoside drugs over the past decade demonstrates that this class of compounds still possesses strong potential [1,2]. The potential of nucleosides in chemotherapy is enhanced by development of new chemistries for nucleoside modification, better understanding of molecular mechanisms of nucleoside drugs’ actions [4], and pro‐drug technology [5,6]. One of the new developments in the medicinal chemistry of nucleosides is nucleoside derivatives comprising a boron component [7]. The boron part can contain a single boron atom [8] or several boron atoms in the form of a boron cluster (Figure 1.2.1) [9–11]. Boron‐containing nucleosides were originally designed as prospective boron carriers for boron neutron capture therapy (BNCT) of tumors [10]. As boron‐rich donors in boron‐carrying molecules, dicarba‐closo‐dodecaboranes (C2B10H12) (1–3) are frequently used due to their chemical and biological stability and physicochemical versatility. More recently, dodecaborate [(B12H12)] (4) and metallacarboranes such as 3-cobalt-bis (1,2‐dicarbollide)ate [Co(C2B9H11)2] (4) (Figure 1.2.1), complexes of carboranes and Boron Cluster Modifications with Antiviral, Anticancer, and Modulation of Purinergic Receptors’ Activities Based on Nucleoside Structures","PeriodicalId":124832,"journal":{"name":"Boron-Based Compounds","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121970323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

New Boronated Compounds for an Imaging-Guided Personalized Neutron Capture Therapy 用于成像引导个性化中子俘获治疗的新型硼化化合物

Boron-Based Compounds Pub Date : 2018-07-12 DOI: 10.1002/9781119275602.CH3.5

N. Protti, A. Deagostino, P. Boggio, D. Alberti, S. G. Crich

引用次数: 2

Recent Advances in Boron Delivery Agents for Boron Neutron Capture Therapy (BNCT) 硼中子俘获治疗(BNCT)中硼递送剂的研究进展

Boron-Based Compounds Pub Date : 2018-07-12 DOI: 10.1002/9781119275602.CH3.2

Sunting Xuan, M. G. H. Vicente

引用次数: 14

Boronic Acid-Based Sensors for Determination of Sugars 基于硼酸的糖测定传感器

Boron-Based Compounds Pub Date : 2018-07-12 DOI: 10.1002/9781119275602.CH2.3

I. Sivaev, V. Bregadze

引用次数: 1

Nanostructured Boron Compounds for Boron Neutron Capture Therapy (BNCT) in Cancer Treatment 用于硼中子俘获治疗(BNCT)癌症的纳米结构硼化合物

Boron-Based Compounds Pub Date : 2018-07-12 DOI: 10.1002/9781119275602.CH3.4

Shanmin Gao, Yinghuai Zhu, N. Hosmane

引用次数: 8

Ionic Boron Clusters as Superchaotropic Anions 离子硼簇作为超向混沌阴离子

Boron-Based Compounds Pub Date : 2018-07-12 DOI: 10.1002/9781119275602.ch1.5

Khaleel I. Assaf, Joanna Wilińska, D. Gabel

{"title":"Ionic Boron Clusters as Superchaotropic Anions","authors":"Khaleel I. Assaf, Joanna Wilińska, D. Gabel","doi":"10.1002/9781119275602.ch1.5","DOIUrl":"https://doi.org/10.1002/9781119275602.ch1.5","url":null,"abstract":"Boron clusters have become key units in various research fields, ranging from material science to medicine [1,2]. Cage‐like boron clusters (Figure 1.5.1) can be classified as closo‐, nido‐, arachno‐, hypho‐, and so on based on the completeness of the polyhedron, with the closo‐ cluster being closed. With one or two missing vertices, boron clusters are named nido‐ or arachno‐, respectively. They have characteristic three‐dimensional pol‐ yhedral geometries, with delocalized electron‐deficient structures [3–6]. Boron clusters, in their neutral and ionic forms, have shown a unique stability and low toxicity [3,4,6,7]. The ability of the 10B isotope to emit α particles after absorbing neutrons makes them ideal for pharmaceutical and medical applications, in particular for boron neutron cap‐ ture therapy (BNCT) [8–10]. Boron clusters interact with biomolecules, including biomembranes and proteins. This offers more possibilities in medicinal use than just BNCT. In this chapter, we sum‐ marize the current research on the noncovalent interactions of common boron clusters, in particular ionic ones, with supramolecular macrocycles, lipid bilayers, and proteins. We draw conclusions for drug design, and point out areas of future research. Polyhedral boron clusters can be divided into neutral and anionic ones. Neutral clus‐ ters include o‐, p‐, and m‐carboranes (C2B10H12). These isomers are highly hydrophobic. Closo‐dodecaborates (B12X12) are water‐soluble dianionic clusters with icosahedral structure, and they are nontoxic anions [11]. Shortly after their discovery, they were introduced as potential BNCT agents [12,13]. The decahydro‐closo‐decaborate anion (B10X10) is another member of the BnHn clusters; it is water‐soluble as sodium salt. Metalla bisdicarbollides, a different class of anionic boron clusters, are sandwiches of two [C2B9H11] (biscarbollide) clusters with a metal ion in the center (e.g., cobalta bis‐ dicarbollide anions); these clusters have recently emerged in medicinal chemistry as HIV protease inhibitors [14–16]. Ionic Boron Clusters as Superchaotropic Anions: Implications for Drug Design","PeriodicalId":124832,"journal":{"name":"Boron-Based Compounds","volume":"30 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132678403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Quantum Mechanical and Molecular Mechanical Calculations on Substituted Boron Clusters and Their Interactions with Proteins 取代硼团簇及其与蛋白质相互作用的量子力学和分子力学计算

Boron-Based Compounds Pub Date : 2018-07-12 DOI: 10.1002/9781119275602.CH1.6

J. Fanfrlík, Adam Pecina, J. Řezáč, P. Hobza, M. Lepšík

{"title":"Quantum Mechanical and Molecular Mechanical Calculations on Substituted Boron Clusters and Their Interactions with Proteins","authors":"J. Fanfrlík, Adam Pecina, J. Řezáč, P. Hobza, M. Lepšík","doi":"10.1002/9781119275602.CH1.6","DOIUrl":"https://doi.org/10.1002/9781119275602.CH1.6","url":null,"abstract":"Medicinal chemistry entails not only synthesis but also compound design. The role of rational drug design has been boosted in recent decades through the use of computer‐ aided drug design, either ligand‐ or structure‐based [1]. The former area makes heavy use of statistics and chemi‐informatics to set up dependencies between the physicochemical properties of the compounds and their biological activities. Although some properties, such as the lipophilicity (expressed as the n‐octanol/water partition coefficient, logP), can also be evaluated computationally by quantum mechanical (QM) or molecular mechanical (MM) methods, ligand‐based drug design is not the focus of this chapter. On the contrary, we discuss here structure‐based drug design, which uses three‐ dimensional (3D) structures of protein–ligand complexes to estimate affinities. The geometries are most often determined experimentally by X‐ray crystallography or nuclear magnetic resonance (NMR). In computer‐aided structure‐based drug design, the ligand’s binding pose within the protein is predicted by docking, a task that has practically been mastered for the broad organic chemistry space [2]. Scoring is thereafter used to assess which of the poses represent the native complex and to rank the compounds by affinity. In contrast, this task has, until recently, been deemed unsolved [3]. We have approached the low reliability of scoring by developing a QM‐based scoring function [4]. Its fundamental principle is QM treatment of protein–ligand noncovalent interactions and solvation [5]. We showed that such an approach can be advantageously used to unequivocally identify the ligand native pose [6], reproduce binding affinity in a series of ligands to various protein targets [5], and describe nonclassical noncovalent interactions, such as halogen bonds [7] or even covalently binding inhibitors [8]. Based on this extensive experience of ours with organic ligands and a decade‐long experience with calculations of boron clusters bound to proteins [9], we affirm that QM scoring is a general solution to the affinity prediction of boron cluster/protein binding. Quantum Mechanical and Molecular Mechanical Calculations on Substituted Boron Clusters and Their Interactions with Proteins Jindřich Fanfrlík, Adam Pecina, Jan Řezáč, Pavel Hobza, and Martin Lepšík*","PeriodicalId":124832,"journal":{"name":"Boron-Based Compounds","volume":"79 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133258341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0