Bøger i QSAR in Environmental and Health Sciences serien

As a result of new statistical and mathematical approaches, improved visualization tools, and recognition by international regulatory groups, quantitative structure-activity relationships (QSARs) now play important roles in pharmacology for the design of new drugs as well as in toxicology and ecotoxicology for hazard identification and risk assessment. Providing up-to-date coverage of the field, Three Dimensional QSAR: Applications in Pharmacology and Toxicology presents the most recent QSAR methods and illustrates their scope, advantages, and limitations. Part I The first part of the book addresses CoMFA and related methods, such as CoMSIA, FLUFF, SOMFA. It also describes shape-, surface-, and volume-based approaches, including MSA, excluded volume, LIV, HASL, receptor surface model, COMPASS, and CoMSA.Part II Focusing on methods that use 3D information, the second part covers autocorrelation methods, such as GRIND; similarity-based methods, including similarity matrices and quantum similarity indices; and quantitative spectroscopic dataΓÇôactivity relationships. Some applications in data mining are also explored.Part III The third part deals with post-3D models. The authors discuss the adaptation of the receptor and simultaneous presence of several conformers or solvation mechanisms.Part IV The final part presents receptor-related approaches as well as docking and free energy calculations, which are treated at various levels. This part concerns the extensive sampling of phase space and approximate methods, such as linear interaction energy, PoissonΓÇôBoltzmann, and generalized Born models. A case study covering several parallel approaches is also developed.An appendix offers the basic principles of modeling and statistical tools routinely required in QSAR methodologies, includi

Juvenile hormones (JHs) are a group of structurally related sesquiterpenes secreted by the insect corpora allata. They affect most insect life-cycle stages and physiological functions, including embryogenesis, larval and adult development, metamorphosis, reproduction, metabolism, diapause, polyethism, and migration. Juvenoids such as methoprene, hydroprene, kinoprene, pyriproxyfen, and fenoxycarb are man-made chemicals that mimic the structure and/or activity of JHs, selectively targeting and disrupting the endocrine system of insects. They are particularly suited as larvicides for the control of pest and disease vectoring insects such as mosquitoes.Juvenile Hormones and Juvenoids: Modeling Biological Effects and Environmental Fate discusses the various modeling approaches that can be used to study the mechanism of action of JHs in insects and to estimate the adverse effects and the environmental fate of the juvenoids that mimic their activity. This book is the third of the QSAR in Environmental and Health Sciences series, but the first dedicated to the use of QSAR and other in silico techniques to provide these insights into JHs and their analogs.With contributions by an international team of scientists, the book begins with a historical survey of JHs and juvenoids. It then discusses biosynthesis of sesquiterpenoids followed by chapters covering JH activity such as morph-specific JH titers in crickets, and JH analog activity including soldier-specific organ development in termites and the role of methoprene in gene transcription. The book examines modeling approaches applied to resistance to JH analogs, to population dynamics of nontarget species in the presence of juvenoids, and to SAR and QSAR of JH mimics. The book concludes with a discussion on the use of multicriteria analysis for selecting insecticides for vector control.

There is a compelling need for new drugs and efficient treatments against mosquito-borne diseases. Computational Design of Chemicals for the Control of Mosquitoes and Their Diseases explains how the search for new substances effective against mosquitoes and their diseases has benefited from the use of in silico techniques.

The pKa of a compound describes its acidity or basicity and, therefore, is one of its most important properties. Its value determines what form of the compoundΓÇöpositive ion, negative ion, or neutral speciesΓÇöwill be present under different circumstances. This is crucial to the action and detection of the compound as a drug, pollutant, or other active chemical agent. In many cases it is desirable to predict pKa values prior to synthesizing a compound, and enough is now known about the salient features that influence a moleculeΓÇÖs acidity to make these predictions.Computational Approaches for the Prediction of pKa Values describes the insights that have been gained on the intrinsic and extrinsic features that influence a moleculeΓÇÖs acidity and discusses the computational methods developed to estimate acidity from a compoundΓÇÖs molecular structure. The authors examine the strengths and weaknesses of the theoretical techniques and show how they have been used to obtain information about the acidities of different classes of chemical compounds.The book presents theoretical methods for both general and more specific applications, covering methods for various acids in aqueous solutionsΓÇöincluding oxyacids and related compounds, nitrogen acids, inorganic acids, and excited-state acidsΓÇöas well as acids in nonaqueous solvents. It also considers temperature effects, isotope effects, and other important factors that influence pKa. This book provides a resource for predicting pKa values and understanding the bases for these determinations, which can be helpful in designing better chemicals for future uses.

Building from the perspective of reproductive and developmental biology, this book provides a timely and comprehensive overview of computational approaches in reproductive and developmental toxicology. It is divided into three broad sections. The first provides a review of methods and approaches to meet the need for safety assessments in product development and regulatory approaches for environmental chemicals. The next section reviews the biological processes and endpoints involved in reproduction and development. The final and largest section summarizes protocols for evaluating biological processes and endpoints within reproduction and development. It also discusses informatics resources and computational methods.

The acidity or basicity of a compound under various conditions is a crucial property for the action and detection of the compound as a drug, pollutant, or other active chemical agent. Thus, the ability to predict pKa values using theoretical methods is extremely useful. This book describes the insights that have been gained on the intrinsic and extrinsic features that influence a molecule¿s acidity and examines the computational methods developed to estimate acidity from a compound¿s molecular structure. It presents techniques for both general and specific applications.

The quantitative structure-activity relationships (QSAR) continue to evolve quickly with an explosion of various tools and techniques. This book addresses the scope and limitations of different modeling techniques using case studies from pharmacology, toxicology, and ecotoxicology to demonstrate the utility of each technique.

Presents an overview of approaches for modeling the endocrine activity of chemicals and the adverse effects they may induce on environmental and human health. This work focuses on chemicals accidentally released into the environment and also on the design, in agro-chemistry, of chemicals acting on the endocrine system of insects to control them.