Antifungal Compounds Discovery

Fungi are both the cause of many major health problems and an incredible source of compounds for developing new medicinal treatments, and with the increasing emergence of multidrug resistance, the need for new antimicrobial agents is greater than ever. Antifungal Compounds Discovery provides researchers with a detailed study of both natural and synthetic compounds that can be effective against a variety of fungal species, supporting and encouraging the design of innovative, potent new drug candidates for the treatment of fungal infections. Beginning with an introduction to both the history and latest developments in this field, the book goes on to provide helpful background information on key fungal species before outlining current antifungal therapies and reasons further development is needed. Detailed chapters then follow reviewing a broad range of natural and synthetic antifungal agents, and discussing the synergistic effect of working with both simultaneously. Finally, the book concludes by considering potential future developments in this important field. Supported with detailed schemes and key information on the biological activity of all selected compounds, Antifungal Compounds Discovery is a comprehensive guide helping researchers understand the relationship between specific chemical structures and their antifungal potency, and a key tool for all those involved in the identification and development of antimicrobial compounds. Provides an overview of the most specific mycotic infections and fungal species as background for compound development Presents the chemical formulas of all natural and synthetic compounds reviewed Combines detailed information about origin, isolation and possible therapeutic uses of all indexed compounds, including biological activity, mechanism of action and SAR information

V. 1- Discovery, developments, and uses; v. 2 - Interactions in biological and ecological systems.

Explores how new molecular technologies are interfacing with chemistry and biology in the search for new fungicide targets.

Fungi are eukaryotic microorganisms that are closely related to humans at cellular level. Human fungal pathogens belong to various classes of fungi, mainly zygo- cetes, ascomycetes, basidiomycetes, and deuteromycetes. In recent years, fungal infections have dramatically increased as a result of improved diagnosis, high frequency of catheterization, instrumentation, etc. However, the main cause remains the increasing number of immunosuppressed patients, mostly because of HIV infection and indiscriminate usage of antineoplastic and immunosuppressive agents, broad-spectrum antibiotics and prosthetic devices, and grafts in clinical settings. Presently available means of combating fungal infections are still weak and clumsy compared to control of bacterial infection. The present scenario of antifungal therapy is still based on two classes of antifungal drugs (polyenes and azoles). These drugs are effective in many cases, but display toxicity and limited spectrum of ef?cacy. The recent trend towards emergence of drug-resistant isolates in the clinic is an additional problem. In recent years, a few new antifungal drugs have entered the clinics, but they are expected to undergo same fate as the older antifungal drugs. The application of fungal genomics offers an unparalleled opportunity to develop novel antifungal drugs. However, it is too early to expect any novel drugs, as the antifungal drug discovery program is in the stage of infancy. Interestingly, several novel antifungal drug targets have been identi?ed and validated.

Fungal infections such as candidoses can range from superficial mucous membrane infection to life-threatening systemic mycoses. Candida infections are a significant clinical problem globally due to rapid rise in compromised host populations including HIV/AIDS, organ transplant recipients and patients on chemotherapy. In addition, sharp increase in aging populations which are susceptible to fungal infections is expected in next few decades. Antifungal drugs are relatively difficult to develop compared to the antibacterial drugs owing to the eukaryotic nature of the cells. Therefore, only a handful of antifungal agents are currently available to treat the myriad of fungal infections. Moreover, rising antifungal resistance and host-related adverse reactions have limited the antifungal arsenal against fungal pathogens. In this research topic, we tried to update the theoretical aspects pertaining to the antifungal drug discovery i.e. proposed novel mechanisms, new drug targets and pathways. In addition, invited authors explored the new antifungal drugs derived from natural and synthetic sources which are currently under development. Contributors were encouraged to bring new insight into the antifungal drug discovery. We hope the reader may arrive at a general consensus on the possible strategies to combat ever increasing ubiquitous fungal infection in this new century.

Resistance is on the rise among a variety of human pathogenic microorganisms associated with common and potentially life-threatening infections, including penicillin-resistant Streptococcus pneumonia and Methicillin-resistant Staphylococcus aureus (MRSA). There is increasing demand to approach the threat of multidrug resistance incorporating novel multidisciplinary methodologies and technological platforms. This book documents the latest research, covering current and promising activities in four key areas: computational chemistry and chemoinformatics, High Throughput Screening (HTS), non-vertebrate model hosts and light and nano-based technologies. It is essential reading for researchers and students in microbiology, biotechnology, pharmacology, chemistry and biology as well as medical professionals.

The most comprehensive source of the latest information in drug discovery and medicinal chemistry BURGER'S MEDICINAL CHEMISTRY AND DRUG DISCOVERY, FIFTH EDITION, Volume 2: Therapeutic Agents Renowned for its incisive, systematic examination of the new classes of drugs, Burger's Medicinal Chemistry and Drug Discovery provides professionals with thorough, yet selective access to drug chemistry information in a convenient format. Volume 2 outlines the newest generation of drugs with the potential for controlling cardiovascular, gastrointestinal, and tubercular disease. These include: * Cholinergics and anticholinergics * Gastric proton pump inhibitors * Cardiac drugs and antihypertensive agents * Diuretic and urcosuric agents * Aminoglycoside, macrolide, glycopeptide, and other antibacterial antibiotics * Antimycobacterial and antifungal agents The behavior of each drug class is explored in terms of pathophysiology of the disease state, molecular mechanism of action, pharmacokinetics, toxicity, drug metabolism, and structure activity relationships. Special attention is given to fertile areas of further research. Burger's Medicinal Chemistry and Drug Discovery, Volume 2 is an essential reference for medical professionals and researchers working today. Burger's Medicinal Chemistry, Fifth Edition consists of five volumes: Volume 1: Principles and Practice (0-471-57556-9) 1995 " . . . an essential addition to the libraries of any medicinal chemist . . . an outstanding work . . . highly praised as a fountain of information in drug studies and research."--Journal of Medicinal Chemistry * Volume 2: Therapeutic Agents (0-471-57557-7) 1996 * Volume 3: Therapeutic Agents (0-471-57558-5) 1996 * Volume 4: Therapeutic Agents (0-471-57559-3) 1997 * Volume 5: Therapeutic Agents (0-471-57560-7) 1997

Drug discovery is a vast area of research due to increase in bacterial and fungal resistance against available drugs. This book will give the basic concepts of Schiff-Mannich Base derivatives of Benzimidazole, Metal complexes and their application in the field of drug discovery. It will also provide the basic mechanistic study as well as the knowledge about characterization techniques which will be helpful for young students and researchers to have a deep insight about Antibacterial and Antifungal agents.

Reviews research on the chemotherapy of fungal diseases, which has progressed at a much slower rate than that against bacterial diseases. Emphasizes the search during the past decade for selective targets of therapeutic agents, selection being the main difficulty because of the eukaryotic nature of fungi. In addition to several novel drugs, considers structures, processes, and proteins as potential targets; and new approaches such as antifungal agents from plants, and genetic methods of drug discovery. Annotation copyrighted by Book News, Inc., Portland, OR

Impedance-based de-replication of antifungal drug classes High-throughput target-based drug screening of synthetic molecules so far has not resulted in new antifungal drug classes. One of the proposed reasons for this failure is the lack of penetration of synthetic molecules in the fungal cell, the high false-positive rates and the lack of selectivity. Three major classes of antifungal drugs are currently in use; the polyenes, the echinocandins and the azoles. Two of them, the polyenes and the echinocandins, are natural products or based on natural products produced by micro-organisms. Small molecules produced by micro-organisms have several desirable characteristics. First, they are highly specific due to their high degree of chirality. Second, they are intrinsically cell permeable and finally, they occupy a more diverse chemical space. However, natural product-based antifungal drug discovery is associated with a number of technical challenges. Fermentation extracts are composed of complex mixtures containing hundreds or thousands of unknown compounds and concomitantly natural product drug discovery is plagued by a high background of known and/or nuisance compounds. Recent efforts have revealed that the vast majority of micro-organisms are still unable to grow under laboratory conditions, indicating a huge unexplored source of new natural compounds. Mining this so-called u2018microbial dark matteru2019 has recently proven successful in the search for novel antibiotics, but has not been used in the search for novel antifungals. Even though previously uncultured micro-organisms can be a rich source of novel antimicrobials, they still produce known antimicrobials. Therefore, a high-throughput de-replication platform to filter out known or undesirable compounds would decrease costs and time consumption in antifungal drug discovery. We have developed a novel tool that can be used to de-replicate antifungal drug classes in a high-throughput and label-free fashion. This tool is based on multisine electrochemical impedance spectroscopy (EIS). Here, Candida albicans biofilms were grown on modified microtiter plates with gold electrodes coated at the bottom of the plates. Next, the cells were subjected to a small alternating potential inside the wells of the 96 well plates during biofilm development or destruction for 24h. The measurement of the resulting micro-current through the developing biofilm results in a signature profile based on multiple frequency components. When we challenged growing C. albicans biofilms with different antifungals we were able to obtain specific signatures for each class. By comparing the signature profile of unknown compounds with a library of signature profiles of known compounds we were able to identify the antifungal mode-of-action. Impedance based de-replication can become a valuable tool in the next-generation of natural product-based drug discovery platforms.

Emerging Targets in Antibacterial and Antifungal Chemotherapy offers constructive ideas to researchers that could lead to the discovery of entirely new classes of drugs. The authors emphasize new topics rather than review work on known antibacterials and antifungals, and identify new targets--either the rate-limiting component of a biochemical pathway or a component of the pathway that is susceptible to a ``screening'' or ``rational drug design'' approach. Each chapter reviews the biochemical pathway and its place in the cellular scheme in order to place the target in perspective. The authors, a mixture of academic researchers and drug-discovery investigators in pharmaceutical companies, also extend these theoretical concerns into practical applications and suggest useful screening methodologies. The importance of this subject area is demonstrated by the increasing number of papers in the literature that point to potential targets and screening methodologies for new antibacterials. This book also deals with antifungals, investigating the inherent limitations in existing antifungals (many of which are extremely toxic or have only limited efficacy), and pointing to major developments in the discovery of novel antifungals. Emerging Targets in Antibacterial and Antifungal Chemotherapy will be of interest to professional microbiologists, biochemists, and cell biologists in both academic and industrial laboratories.

A collection of state-of-the-art molecular methods for studying antifungal resistance, for discovering and evaluating both new and existing antifungal drugs, and for understanding the host response and immunotherapy of such agents. The protocols follow the successful Methods in Molecular MedicineTM series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. Antifungal Agents: Methods and Protocols offers clinician-scientists, microbiologists and molecular biologists the productive tools they need today to understand and successfully develop new therapeutic agents for yeast, mold, and fungal infections.

The most comprehensive source of the latest information in drug discovery and medicinal chemistry BURGER'S MEDICINAL CHEMISTRY AND DRUG DISCOVERY, FIFTH EDITION, Volume 2: Therapeutic Agents Renowned for its incisive, systematic examination of the new classes of drugs, Burger's Medicinal Chemistry and Drug Discovery provides professionals with thorough, yet selective access to drug chemistry information in a convenient format. Volume 2 outlines the newest generation of drugs with the potential for controlling cardiovascular, gastrointestinal, and tubercular disease. These include: * Cholinergics and anticholinergics * Gastric proton pump inhibitors * Cardiac drugs and antihypertensive agents * Diuretic and urcosuric agents * Aminoglycoside, macrolide, glycopeptide, and other antibacterial antibiotics * Antimycobacterial and antifungal agents The behavior of each drug class is explored in terms of pathophysiology of the disease state, molecular mechanism of action, pharmacokinetics, toxicity, drug metabolism, and structure activity relationships. Special attention is given to fertile areas of further research. Burger's Medicinal Chemistry and Drug Discovery, Volume 2 is an essential reference for medical professionals and researchers working today. Burger's Medicinal Chemistry, Fifth Edition consists of five volumes: Volume 1: Principles and Practice (0-471-57556-9) 1995 " . . . an essential addition to the libraries of any medicinal chemist . . . an outstanding work . . . highly praised as a fountain of information in drug studies and research."--Journal of Medicinal Chemistry * Volume 2: Therapeutic Agents (0-471-57557-7) 1996 * Volume 3: Therapeutic Agents (0-471-57558-5) 1996 * Volume 4: Therapeutic Agents (0-471-57559-3) 1997 * Volume 5: Therapeutic Agents (0-471-57560-7) 1997

An in-depth exploration of the applications of plant bioactive metabolites in drug research and development Highlighting the complexity and applications of plant bioactive metabolites in organic and medicinal chemistry, Plant Bioactives and Drug Discovery: Principles, Practice, and Perspectives provides an in-depth overview of the ways in which plants can inform drug research and development. An edited volume featuring multidisciplinary international contributions from acclaimed scientists researching bioactive natural products, the book provides an incisive overview of one of the most important topics in pharmaceutical studies today. With coverage of strategic methods of natural compound isolation, structural manipulation, natural products in clinical trials, quality control, and more, and featuring case studies on medicinal plants, the book serves as a definitive guide to the field of plant biodiversity as it relates to medicine. In addition, chapters on using natural products as drugs that target specific disease areas, including neurological disorders, inflammation, infectious diseases, and cancer, illustrate the myriad possibilities for therapeutic applications. Wide ranging and comprehensive, Plant Bioactives and Drug Discovery also includes important information on marketing, regulations, intellectual property rights, and academic-industry collaboration as they relate to plant-based drug research, making it an essential resource for advanced students and academic and industry professionals working in biochemical, pharmaceutical, and related fields.

Reviews research on the chemotherapy of fungal diseases, which has progressed at a much slower rate than that against bacterial diseases. Emphasizes the search during the past decade for selective targets of therapeutic agents, selection being the main difficulty because of the eukaryotic nature of fungi. In addition to several novel drugs, considers structures, processes, and proteins as potential targets; and new approaches such as antifungal agents from plants, and genetic methods of drug discovery. Annotation copyrighted by Book News, Inc., Portland, OR

Although science has discovered effective drugs for many of the diseases that afflict mankind, many human health problems remain untreatable. The search for novel therapeutic agents is always ongoing. This book will describe some of the diverse sources of natural products, such as terrestrial and marine environments; and will review how research has increased knowledge of biological systems and human disease, leading to the design of targeted asssays, amenable to high volume screening.