248,407 research outputs found
Guidebook on molecular modeling in drug design /
No full textSpecially designed computer software is revolutionizing procedures for structured or rational drug design and discovery. The Guidebook on Molecular Modeling in Drug Design serves as a manual for the analysis ofmolecular structure and the correlation of these structures with pharmacological reactions. Intended as an introductory guide for advanced students and professionals with an interest in computer-assisted modeling for drug design and discovery, this bookwill also be of interest to medicinal and organic chemists, pharmaceutical researchers, pharmacologists, and biochemists who want to gain further insight into this rapidly advancing field. Molecular modeling is assuming an important role in the understanding of three-dimensional aspects in the specificity of drug-receptor interactions at the molecular level. This research area has become a well-established discipline in pharmaceutical research. It has created unprecedented opportunities in assisting medicinal chemists in the design of new therapeutic agents. Advances made in computer hardware and in theoretical medicinal chemistry have brought high-performance computing and graphics tools within reach of most academic and industrial laboratories, facilitating the development of useful approaches to rational drug design. The Guidebook on Molecular Modeling in Drug Design serves as a manual for the analysis of the molecular structure of biological molecules and drugs and the correlation of these structures with pharmacological actions. Intended as a guide for advanced students and professionals with an interest in computer-assisted modeling for drug design and discovery, this book will also be of interest to medicinal and organic chemists, pharmaceutical researchers, pharmacologists, and biochemists who want to gain further insight into this rapidly advancing field.Specially designed computer software is revolutionizing procedures for structured or rational drug design and discovery. The Guidebook on Molecular Modeling in Drug Design serves as a manual for the analysis ofmolecular structure and the correlation of these structures with pharmacological reactions. Intended as an introductory guide for advanced students and professionals with an interest in computer-assisted modeling for drug design and discovery, this bookwill also be of interest to medicinal and organic chemists, pharmaceutical researchers, pharmacologists, and biochemists who want to gain further insight into this rapidly advancing field. Molecular modeling is assuming an important role in the understanding of three-dimensional aspects in the specificity of drug-receptor interactions at the molecular level. This research area has become a well-established discipline in pharmaceutical research. It has created unprecedented opportunities in assisting medicinal chemists in the design of new therapeutic agents. Advances made in computer hardware and in theoretical medicinal chemistry have brought high-performance computing and graphics tools within reach of most academic and industrial laboratories, facilitating the development of useful approaches to rational drug design. The Guidebook on Molecular Modeling in Drug Design serves as a manual for the analysis of the molecular structure of biological molecules and drugs and the correlation of these structures with pharmacological actions. Intended as a guide for advanced students and professionals with an interest in computer-assisted modeling for drug design and discovery, this book will also be of interest to medicinal and organic chemists, pharmaceutical researchers, pharmacologists, and biochemists who want to gain further insight into this rapidly advancing field.N.C. Cohen, Preface. N.C. Cohen, The Molecular Modeling Perspective in Drug Design. R.E. Hubbard, Molecular Graphics and Modeling: The Tools of the Trade. T. Gund, Molecular Modeling of Small Molecules. A. Itai, M.Y. Mitzutani, and Y. Nishibata, Computer-Assisted New-Lead Design. J. Priestle and G. Paris, Experimental Techniques and Data Banks. P. Gund, G. Maggiora, and J.P. Snyder, Computer-Assisted Drug Discovery. M. Clare, S. Rao, and J.P. Snyder, Modeling Drug-Receptor Interactions. J.P. Tollenaere, Glossary of Terminology. Index.Includes bibliographical references and index.Print version record.Electronic reproduction.Master and use copy. Digital master created according to Benchmark for Faithful Digital Reproductions of Monographs and Serials, Version 1. Digital Library Federation, December 2002.digitizedElsevie
Exploring Polypharmacology in Drug Design
No full textNowadays it is widely accepted that one compound can be able to hit several targets at once. This “magic shotgun” approach for drug development properly describes the mechanism of biomolecular recognition. The need to take into account the polypharmacology in structure-based drug design has led to the development of several computational tools. Here we present a computational protocol to identify promising compounds against several biological targets, a protocol known as inverse docking. © Springer Science+Business Media, LLC, part of Springer Nature 2018
Protein-Ligand Interactions and Drug Design
No full textThis detailed book collects modern and established computer-based methods aimed at addressing the drug discovery challenge from disparate perspectives by exploiting information on ligand-protein recognition. Beginning with methods that allow for the exploration of specific areas of chemical space and the designing of virtual libraries, the volume continues with sections on methods based on docking, quantitative models, and molecular dynamics simulations, which are employed for ligand discovery or development, as well as methods exploiting an ensemble of protein structures for the identification of potential protein targets. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Protein-Ligand Interactions and Drug Design provides detailed practical procedures of solid computer-aided drug design methodologies employed to rationalize and optimize protein-ligand interactions, for experienced researchers and novices alike.</p
Advances in antiviral drug design.
No full textVolume 3 of Advances in Antiviral Drug Design is keeping up with the recent progress made in the field of antiviral drug research and highlights five specific directions that have opened new avenues for the treatment of virus infections. First, the use of lamivudine (3TC) for the treatment of HIV infections, and its more recent introduction for the treatment of hepatitis B virus (HBV) infections, has heralded the transition of D- to L-nucleosides in the antiviral nucleoside drug design, and it is likely that the future will provide more nucleosides of the L-configuration, such as ( - )FFC (emtricitabine) and L-FMAU, as will be described by J.-C.G. Graciet and R.F. Shinazi. Second, the acyclic purine nucleoside phosphonates, i.e. PMEA (adefovir and PMPA (tenofovir), offer great potential as both anti-HIV and anti-HBV agents, and both compounds have been the subject of advanced clinical trials in their oral produrg form (adefovir dipivoxil and tenofovir disoproxyl), as mentioned by M.N. Arimilli, J.P. Dougherty, K.C. Cundy, and N. Bischofberger. Third, with the advent of nevirapine, delavirdine, and efavirenz, the NNRTIs have definitely come of age. Emivirine (MKC-442), a derivative of the original HEPT analog that was described in 1989 has now proceeded through pivotal clinical studies, and how this class of compounds evolved is presented in the account of H. Tanaka and his colleagues. Fourth, at the end of 1999, anticipating on the next winter influenza offensive, we should have at end two compounds that specifically inhibit influenza A and B virus infections: zanamivir (by the intranasal route) and oseltamivir (by the oral route). Both compounds have proved effective in the prophylaxis and treatment of influenza A and B virus infections and act through the same mechanism; that is by blocking the viral neuraminidase (or sialidase), a key enzyme that allows the virus to spread from one cell to another (within the respiratory mucosal tract). The design of these sialidase inhibitors will be presented by M. von Itzstein and J.C. Dyason. Fifth, the discovery (in 1996) of the chemokine receptors CXCR4 and CCR5 as essential coreceptors (in addition to the CD4 receptor) for HIV entry into the cells, has boosted an enormous interest in potential antagonists of these receptors. The bicyclams represent the first low-molecular-weight compounds targeted at CXCR4, the coreceptor used by the more pathogenic, T-lymphotropic, HIV strains, to enter the cells. They will be addressed by G.J. Bridger and R.T. Skerlj. The five topics covered in this third volume of Advances in Antiviral Drug Design are in the front line of the present endeavors towards the chemotherapy of virus infections. They pertain to the combat against three of the most important virus infections of current times: HIV, HBV, and influenza virus.Volume 3 of Advances in Antiviral Drug Design is keeping up with the recent progress made in the field of antiviral drug research and highlights five specific directions that have opened new avenues for the treatment of virus infections. First, the use of lamivudine (3TC) for the treatment of HIV infections, and its more recent introduction for the treatment of hepatitis B virus (HBV) infections, has heralded the transition of D- to L-nucleosides in the antiviral nucleoside drug design, and it is likely that the future will provide more nucleosides of the L-configuration, such as ( - )FFC (emtricitabine) and L-FMAU, as will be described by J.-C.G. Graciet and R.F. Shinazi. Second, the acyclic purine nucleoside phosphonates, i.e. PMEA (adefovir and PMPA (tenofovir), offer great potential as both anti-HIV and anti-HBV agents, and both compounds have been the subject of advanced clinical trials in their oral produrg form (adefovir dipivoxil and tenofovir disoproxyl), as mentioned by M.N. Arimilli, J.P. Dougherty, K.C. Cundy, and N. Bischofberger. Third, with the advent of nevirapine, delavirdine, and efavirenz, the NNRTIs have definitely come of age. Emivirine (MKC-442), a derivative of the original HEPT analog that was described in 1989 has now proceeded through pivotal clinical studies, and how this class of compounds evolved is presented in the account of H. Tanaka and his colleagues. Fourth, at the end of 1999, anticipating on the next winter influenza offensive, we should have at end two compounds that specifically inhibit influenza A and B virus infections: zanamivir (by the intranasal route) and oseltamivir (by the oral route). Both compounds have proved effective in the prophylaxis and treatment of influenza A and B virus infections and act through the same mechanism; that is by blocking the viral neuraminidase (or sialidase), a key enzyme that allows the virus to spread from one cell to another (within the respiratory mucosal tract). The design of these sialidase inhibitors will be presented by M. von Itzstein and J.C. Dyason. Fifth, the discovery (in 1996) of the chemokine receptors CXCR4 and CCR5 as essential coreceptors (in addition to the CD4 receptor) for HIV entry into the cells, has boosted an enormous interest in potential antagonists of these receptors. The bicyclams represent the first low-molecular-weight compounds targeted at CXCR4, the coreceptor used by the more pathogenic, T-lymphotropic, HIV strains, to enter the cells. They will be addressed by G.J. Bridger and R.T. Skerlj. The five topics covered in this third volume of Advances in Antiviral Drug Design are in the front line of the present endeavors towards the chemotherapy of virus infections. They pertain to the combat against three of the most important virus infections of current times: HIV, HBV, and influenza virus.List of Contributors. Preface. From D- to L-nucleoside analogs as antiviral agents. Orally bioavailable acyclic nucleoside phosphonate prodrugs: adefovir dipivoxil and BIS(POC)PMPA. HEPT: from an investigation of lithiation of nucleosides towards a rational design of non-nucleoside reverse transcriptase inhibitors of HIV-1). Sialidase inhibitors as anti-influenza drugs. Bicyclam derivatives as HIV inhibitors. Index.Réf. bibliogr. Index.Print version record.Elsevie
Computer-Aided Drug Design for AMP-Activated Protein Kinase Activators
No full textAMP-activated protein kinase (AMPK) is an important therapeutic target for the potential treatment of metabolic disorders, cardiovascular disease and cancer. Recently, various classes of compounds that activate AMPK by direct or indirect interactions have been reported. The importance of computer-aided drug design approaches in the search for potent activators of AMPK is now established, including structure-based design, ligand-based design, fragment-based design, as well as structural analysis. This review article highlights the computer-aided drug design approaches utilized to discover of activators targeting AMPK. The principles, advantages or limitation of the different methods are also being discussed together with examples of applications taken from the literatures.Chemistry, MedicinalComputer Science, Interdisciplinary ApplicationsSCI(E)0ARTICLE3214-227
Alterated expression of extra-cellular matrix proteins and integrin receptors in discoid lupus erythematosus
No full textAlterated expression of extra-cellular matrix proteins and integrin receptors in discoid lupus erythematosus
No full textMacrocycles in Drug Discovery
No full textMacrocycles are a ring architecture of 12 or more atoms that allows them to highly dynamically adapt to large receptor surfaces, e.g. in protein–protein interactions (PPIs). Macrocycles cover the chemical space between small molecules and monoclonal antibodies (mABs) and potentially combine the best of the two worlds. Recent progress in the synthetic accessibility of the macrocycle space (e.g. DEL, MCR) open new opportunities to answer pressing questions in the field: What is the relationship between the 2D space and the 3D conformational hyperspace and drug-like properties? How can drug-like properties be designed into macrocyclic structures? What structural features will help to increase passive membrane permeation? Can design rules be elaborated to increase the drug likeliness of macrocycles? How can the success rate of virtual screening methods for macrocycles be enhanced? Much greater understanding of the relationship between the conformational and biological space must be generated. Such knowledge will propel macrocycles into the league of next generation drugs. Novel design and synthetic strategies to provide different classes of macrocycles will grow the impact of macrocyles on drug discovery. This Special Issue aims to highlight multiple aspects of macrocycles, from synthetic chemistry to conformational design, to applications in drug discovery and computational screening methods
Structure-Activity Relationships (SAR) Research of Thiourea Derivatives as Dual Inhibitors Targeting both HIV-1 Capsid and Human Cyclophilin A
No full textHIV-1 capsid (CA) and human cyclophilin A (CypA) play important roles in HIV-1 assembly and disassembly processes, which are critical in HIV-1 replication. Based on the discovery of thiourea derivatives targeting both of the two proteins and indicating effective inhibitory activities in our group, we designed and synthesized a new class of thiourea derivatives. Their abilities to bind to capsid and cyclophilin A were determined by ultraviolet spectroscopic analysis, fluorescence binding affinity, and PPIase inhibition assay. Furthermore, the newly synthesized compounds were tested for their antiviral activities and cytotoxicities using CEM cells. According to the biological evaluation and subsequent molecular docking analyses, we studied the structure-activity relationships of thiourea derivatives. Three optimal compounds (K17, K24, K25) based on the achieved structure-activity relationships would be the basis for future optimization.Biochemistry & Molecular BiologyChemistry, MedicinalSCI(E)PubMed7ARTICLE125-337
Synthesis and Antiviral Evaluation of New N-acylhydrazones Containing Glycine Residue
No full textN-acylhydrazones containing glycine residue 3a-j and 8a-h were synthesized as HIV-1 capsid protein assembly inhibitors. The structures of the novel N-acylhydrazone derivatives were characterized using different spectroscopic methods. Antiviral activity demonstrated that compound 8c bearing 4-methylphenyl moiety was the most active with low cytotoxicity.Biochemistry & Molecular BiologyChemistry, MedicinalSCI(E)PubMed6ARTICLE3189-1987
- …
