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Drug Discovery Targeting Drug Resistant Bacteria

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Drug Discovery Targeting Drug Resistant Bacteria

Drug Discovery Targeting Drug Resistant Bacteria Book
Author : Prashant Kesharwani,Sidharth Chopra,Arunava Dasgupta
Publisher : Academic Press
Release : 2020-05
ISBN : 0128184809
Language : En, Es, Fr & De

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Book Description :

Drug Discovery Targeting Drug-Resistant Bacteria explores the status and possible future of developments in fighting drug-resistant bacteria. The book covers the majority of microbial diseases and the drugs targeting them. In addition, it discusses the potential targeting strategies and innovative approaches to address drug resistance. It brings together academic and industrial experts working on discovering and developing drugs targeting drug-resistant (DR) bacterial pathogens. New drugs active against drug-resistant pathogens are discussed, along with new strategies being used to discover molecules acting via new modes of action. In addition, alternative therapies such as peptides and phages are included. Pharmaceutical scientists, microbiologists, medical professionals, pathologists, researchers in the field of drug discovery, infectious diseases and microbial drug discovery both in academia and in industrial settings will find this book helpful.

Drug Discovery Targeting Drug Resistant Bacteria

Drug Discovery Targeting Drug Resistant Bacteria Book
Author : Prashant Kesharwani,Sidharth Chopra,Arunava Dasgupta
Publisher : Academic Press
Release : 2020-05-15
ISBN : 0128184817
Language : En, Es, Fr & De

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Book Description :

Drug Discovery Targeting Drug-Resistant Bacteria explores the status and possible future of developments in fighting drug-resistant bacteria. The book covers the majority of microbial diseases and the drugs targeting them. In addition, it discusses the potential targeting strategies and innovative approaches to address drug resistance. It brings together academic and industrial experts working on discovering and developing drugs targeting drug-resistant (DR) bacterial pathogens. New drugs active against drug-resistant pathogens are discussed, along with new strategies being used to discover molecules acting via new modes of action. In addition, alternative therapies such as peptides and phages are included. Pharmaceutical scientists, microbiologists, medical professionals, pathologists, researchers in the field of drug discovery, infectious diseases and microbial drug discovery both in academia and in industrial settings will find this book helpful. Written by scientists with extensive industrial experience in drug discovery Provides a balanced view of the field, including its challenges and future directions Includes a special chapter on the identification and development of drugs against pathogens which exhibit the potential to be used as weapons of war

Discovering Antibacterial and Anti resistance Agents Targeting Multi drug Resistant ESKAPE Pathogens

Discovering Antibacterial and Anti resistance Agents Targeting Multi drug Resistant ESKAPE Pathogens Book
Author : Renee Marie Fleeman
Publisher : Unknown
Release : 2017
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Antibiotic resistance has been a developing problem for mankind in recent decades and multi-drug resistant bacteria are now encountered that are resistant to all treatment options available. In 2014, the World Health Organization announced that this problem is driving us towards a “post-antibiotic era” that will change the face of modern medicine as we know it. If lack of novel antibiotic development and FDA approval continues, by the year 2050, 10 million people will die each year to an antimicrobial resistant bacterial infection. With lack of pharmaceutical industry involvement in developing novel antibiotics, the responsibility now lies within the academic institutions to identify potential novel therapeutics to fuel the antibiotic drug discovery pipeline. Combinatorial chemistry is one technique used to expedite the discovery process by assessing a large chemical space in a relatively short time when compared to traditional screening approaches. Combinatorial libraries can be screened using multiple approaches and has shown successful application towards many disease states. We initially discovered broad spectrum antibacterial bis-cyclic guanidines using combinatorial libraries and expanded on the knowledge of the physiochemical attributes necessary to inhibit Gram negative bacterial pathogens. Following this success, we continued to assess the combinatorial libraries for adjunctive therapeutics that potentiate the activity of obsolete clinical antibiotics. The polyamine efflux pump inhibitors discovered in this subsequent study prove the benefits of using the large chemical space provided in the combinatorial libraries to identify a variety of therapeutics. Our studies always begin with identifying an active compound and active compounds undergo hit-to-lead optimization. This optimization studies are of utmost importance in developing a novel antibacterial agent for therapeutic applications. Our medicinal chemistry work described here is proof of the success of careful structure activity analyses to optimize a hit scaffold to create a more effective antibacterial agent. Overall, our work described here reveals the potential role of academic institutions in fending off the impending “post-antibiotic era”.

Make Antibiotics Great Again Combating Drug Resistance by Targeting LexA a Regulator of Bacterial Evolution

Make Antibiotics Great Again  Combating Drug Resistance by Targeting LexA  a Regulator of Bacterial Evolution Book
Author : Charlie Y. Mo
Publisher : Unknown
Release : 2016
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

The ability of bacterial pathogens to evolve and adapt to our antimicrobial agents has precipitated a global health crisis where treatment options for bacterial infections are running low. Recently, studies have shown that the ability to acquire resistance is linked to the SOS response, which is a widely conserved network of genes involved in both high fidelity and error-prone DNA damage repair. The SOS response is regulated by the DNA-binding protein, RecA, and a repressor-protease, LexA. When the cell experiences stress, which can be caused by antibiotics, RecA polymerizes along single-stranded DNA and thereby stimulates LexA to undergo a conformational change and self-cleavage reaction (autoproteolysis). LexA self-cleavage de-represses downstream SOS genes, which are involved in both stress tolerance and mutagenesis. Various studies have shown that inactivating LexA autoproteolysis can both reduce the viability of bacteria under antibiotic stress and impede their ability to acquire resistance. These results therefore suggest that targeting LexA therapeutically could offer a novel way to combat the rise of resistance in pathogens, although to date no LexA inhibitors have been found. To facilitate the development of such therapeutics, we focused our efforts on examining LexA from 1) biochemical, 2) microbiological, and 3) drug discovery perspectives. On the biochemical front, we elucidated the substrate preference of LexA’s serine protease active site to form a better understanding of the target enzyme’s active site architecture. Performing saturation mutagenesis on the LexA’s internal cleavage loop, we showed that LexA possesses a unique active site, revealing residues involved in specific molecular recognition and conformational change. On the microbiological front, we examined how different LexA activities can impact bacterial drug susceptibility and stress-induced mutagenesis. Employing engineered E. coli strains with a spectrum of SOS activities, we showed that modulating LexA activity can increase bacterial susceptibility to antibiotics, while also tuning stress-induced mutagenesis. Finally, on the drug discovery front, we designed a high-throughput screen that enabled us to discover small molecule inhibitors of the LexA/RecA axis in collaboration with GlaxoSmithKline. Together, this work provides a multi-pronged foray into developing therapeutics that target the SOS pathway and combat the rise of antibiotic resistance.

Sustainable Agriculture Reviews 46

Sustainable Agriculture Reviews 46 Book
Author : Harsh Panwar,Chetan Sharma,Eric Lichtfouse
Publisher : Springer Nature
Release : 2020-09-29
ISBN : 3030530248
Language : En, Es, Fr & De

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Book Description :

According to the World Health Organization, antimicrobial resistance is a major threat to global health because the number of alternative antibiotics is very limited. Antimicrobial resistance is a slow evolutionary process that has been accelerated by human activities in health, environment and agriculture sectors. Due to their wide application, antibiotics and their residues have been found in almost all food products and natural ecosystems. This book reviews the drivers, impact and mitigation of antimicrobial resistance, with focus on methods and targets.

Chemical Biology Approaches Towards Cell permeable Inhibitors Targeting Nonribosomal Peptide Biosynthesis

Chemical Biology Approaches Towards Cell permeable Inhibitors Targeting Nonribosomal Peptide Biosynthesis Book
Author : Tony Dwayne Davis,Cornell University. Weill Cornell Graduate School of Medical Sciences
Publisher : Unknown
Release : 2014
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

The emergence of drug-resistant bacteria presents opportunities to develop novel antibacterials that address this area of urgent medical need. Recently, numerous groups have developed potent small-molecule inhibitors targeting essential bacterial adenylation enzymes. However, one factor that hinders the further development of these compounds as potential antibacterials is their lack of cellular activity, presumably due to poor cellular permeability. The permeability of small molecules in bacteria remains elusive and efforts to understand permeability would greatly facilitate future drug discovery efforts in this arena. Herein, we address bacterial permeability on two major fronts. In the first half of this dissertation, we discuss progress towards the design and synthesis of cell-permeable small molecules targeting amino acid adenylation domains that are implicated in the biosynthesis of bacterial siderophores. We employed isosteric replacement and prodrug design to improve cellular permeability. In the second half of this dissertation, we develop a systematic and quantitative platform to understand bacterial small-molecule permeability. We evaluate the accumulation and efflux of a panel of ten structurally-related compounds in three bacteria with cell envelopes of varying complexities. Then, we use cheminformatic analyses to find correlations between structural and physicochemical properties, accumulation, and efflux sensitivity.

Research EU

Research EU  Book
Author : Anonim
Publisher : Unknown
Release : 2012-02
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Research EU book written by , available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Preclinical Antimicrobial Drug Discovery

Preclinical Antimicrobial Drug Discovery Book
Author : Bill Lee
Publisher : Unknown
Release : 2006
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

"The incidence of infections caused by antibiotic-resistant bacteria and fungi is rising rapidly. Once considered as little more than a nuisance, antibiotic resistance has become a serious threat. The mortality rate for some infections is approaching that of the pre-antibiotic era. New antimicrobials are needed urgently. Prior to the introduction of any new antimicrobial, comprehensive toxicity and efficacy profiles are assessed in preclinical studies. This thesis focuses on two key stages of preclinical antimicrobial drug development, specifically compound screening in vitro and animal efficacy testing in vivo. We developed a sensitive colorimetric platform with high-throughput capacity for the rapid screening of candidate antimicrobials. This platform could be adapted to assess compounds targeting a range of bacteria, fungi (such as Candida albicans), and protozoan parasites (such as Leishmania major). When this assay was modified to measure minimum inhibitory concentrations (MICs) for bacteria, 100% agreement within one dilution was achieved compared to the gold-standard method. A novel antifungal compound was taken forward to animal testing in an immunocompromised mouse model. We demonstrated herein that a histone deacetylase inhibitor in combination with an imidazole can synergise to produce a potent antifungal effect. A dose-dependent response, defined as a lower fungal burden and a higher survival rate, was achieved with increasing concentrations of the novel inhibitor." --

Antibacterial Agents

Antibacterial Agents Book
Author : Rosaleen Anderson,Paul Groundwater,Adam Todd,Alan Worsley
Publisher : John Wiley & Sons
Release : 2012-07-23
ISBN : 0470972440
Language : En, Es, Fr & De

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Book Description :

Antibacterial agents act against bacterial infection either by killing the bacterium or by arresting its growth. They do this by targeting bacterial DNA and its associated processes, attacking bacterial metabolic processes including protein synthesis, or interfering with bacterial cell wall synthesis and function. Antibacterial Agents is an essential guide to this important class of chemotherapeutic drugs. Compounds are organised according to their target, which helps the reader understand the mechanism of action of these drugs and how resistance can arise. The book uses an integrated lab–to–clinic approach which covers drug discovery, source or synthesis, mode of action, mechanisms of resistance, clinical aspects (including links to current guidelines, significant drug interactions, cautions and contraindications), prodrugs and future improvements. Agents covered include: agents targeting DNA – quinolone, rifamycin, and nitroimidazole antibacterial agents agents targeting metabolic processes – sulfonamide antibacterial agents and trimethoprim agents targeting protein synthesis – aminoglycoside, macrolide and tetracycline antibiotics, chloramphenicol, and oxazolidinones agents targeting cell wall synthesis – –Lactam and glycopeptide antibiotics, cycloserine, isonaizid, and daptomycin Antibacterial Agents will find a place on the bookshelves of students of pharmacy, pharmacology, pharmaceutical sciences, drug design/discovery, and medicinal chemistry, and as a bench reference for pharmacists and pharmaceutical researchers in academia and industry.

Medicinal Chemistry and Drug Discovery Chemotherapeutic agents

Medicinal Chemistry and Drug Discovery  Chemotherapeutic agents Book
Author : Alfred Burger
Publisher : Unknown
Release : 2003
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Medicinal Chemistry and Drug Discovery Chemotherapeutic agents book written by Alfred Burger, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Frontiers in Anti Infective Drug Discovery

Frontiers in Anti Infective Drug Discovery Book
Author : Atta-ur-Rahman,M. Iqbal Choudhary
Publisher : Bentham Science Publishers
Release : 2015-06-30
ISBN : 1681080826
Language : En, Es, Fr & De

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Book Description :

This eBook series brings updated reviews to readers interested in advances in the development of anti-infective drug design and discovery. The scope of the eBook series covers a range of topics including rational drug design and drug discovery, medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, recent important patents, and structure-activity relationships. Frontiers in Anti-Infective Drug Discovery is a valuable resource for pharmaceutical scientists and post-graduate students seeking updated and critically important information for developing clinical trials and devising research plans in this field. The fourth volume of this series features 5 chapters that cover the following topics: - An overview of the incidence of neuraminadase resistance in influenza viruses in the Americas from 2004 to 2014 - Phenothiazines and derivative compounds for treating Trypanosoma cruzi infections - New antibacterial drug targets such as polysaccharide deacetylases - Improvements in aminoglycoside synthesis and biological activity (including RNA targeting) - A review of new chemotherapeutic agents against common infections.

Frontiers in Clinical Drug Research Anti Infectives Volume 5

Frontiers in Clinical Drug Research   Anti Infectives  Volume 5 Book
Author : Atta-ur-Rahman
Publisher : Bentham Science Publishers
Release : 2019-06-11
ISBN : 1681086387
Language : En, Es, Fr & De

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Book Description :

Frontiers in Clinical Drug Research – Anti infectives is a book series that brings updated reviews to readers interested in learning about advances in the development of pharmaceutical agents for the treatment of infectious diseases. The scope of the book series covers a range of topics including the chemistry, pharmacology, molecular biology and biochemistry of natural and synthetic drugs employed in the treatment of infectious diseases. Reviews in this series also include research on multi drug resistance and pre-clinical / clinical findings on novel antibiotics, vaccines, antifungal agents and antitubercular agents.Frontiers in Clinical Drug Research – Anti infectives is a valuable resource for pharmaceutical scientists and postgraduate students seeking updated and critically important information for developing clinical trials and devising research plans in the field of anti infective drug discovery and epidemiology. The fifth volume of this series features six reviews: - Integrated Approaches for Marine Actinomycete Biodiscovery - Therapeutic Use of Commensal Microbes: Fecal/Gut Microbiota Transplantation - Alternative Approaches to Antimicrobials - Nanoantibiotics: Recent Developments and Future - Cranberry Juice and Other Functional Foods in Urinary Tract Infections in Women: A Review of Actual Evidence and Main Challenges - Targeting Magnesium Homeostasis as Potential Anti-Infective Strategy Against Mycobacteria

Antimicrobial Producing Bacteria as Agents of Microbial Population Dynamics

Antimicrobial Producing Bacteria as Agents of Microbial Population Dynamics Book
Author : Justin Rogers Tanner
Publisher : Unknown
Release : 2010
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

The need for new antibiotics has been highlighted recently with the increasing pace of emergence of drug resistant pathogens (MRSA, XDR-TB, etc.). Modification of existing antibiotics with the additions of side chains or other chemical groups and genomics based drug targeting have been the preferred method of drug development at the corporate level in recent years. These approaches have yielded few viable antibiotics and natural products are once again becoming an area of interest for drug discovery. We examined the antimicrobial "Red Soils" of the Hashemite Kingdom of Jordan that have historically been used to prevent infection and cure rashes by the native peoples. Antimicrobial producing bacteria were present in these soils and found to be the reason for their antibiotic activity. After isolation, these bacteria were found to excrete their antimicrobials into the liquid culture media which we could then attempt to isolate for further study. Adsorbent resins were employed to capture the antimicrobial compounds and then elute them in a more concentrated solution. As part of a drug discovery program, we sought a way to quickly characterize other soils for potential antibiotic producing bacteria. The community level physiologic profile was examined to determine if this approach would allow for a rapid categorizing of soils based on their probability of containing antimicrobial producing microorganisms. This method proved to have a high level of variability that could not be overcome even after mixing using a commercial blender. The role of these antimicrobial producing bacteria within their natural microbial community has largely been confined to microbe-plant interactions. The role of antimicrobial-producing microorganisms in driving the diversity of their community has not been a focus of considerable study. The potential of an antimicrobial-producing bacterium to act as a driver of diversity was examined using an artificial microbial community based in a sand microcosm. The changes in the microbial assemblage indicate that antimicrobial-producing bacteria may act in an allelopathic manner rather than in a predatory role.

The Richard and Hinda Rosenthal Symposium 2014

The Richard and Hinda Rosenthal Symposium 2014 Book
Author : Institute of Medicine
Publisher : National Academies Press
Release : 2014-10-13
ISBN : 0309312892
Language : En, Es, Fr & De

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Book Description :

The Institute of Medicine launched an innovative outreach program in 1988. Through the generosity of the Rosenthal Family Foundation (formerly the Richard and Hinda Rosenthal Foundation), a discussion series was created to bring greater attention to some of the significant health policy issues facing our nation today. Each year a major health topic is addressed through remarks and conversation between experts in the field. The IOM later publishes the proceedings from this event for the benefit of a wider audience. This volume summarizes remarks by and an engaging discussion with Dr. Rima Khabbaz, Dr. Stuart Levy, Dr. Margaret (Peg) Riley, and Dr. Brad Spellberg on "Antimicrobial Resistance: A Problem Without Borders." The Centers for Disease Control and Prevention identified antimicrobial resistance as one of five urgent health threats facing the United States this year. Antimicrobial resistance is a global health security threat that will demand collaboration from many stakeholders around the world. This report highlights the crosscutting character of antimicrobial resistance and the needs for many disciplines to be brought together to be able to deal with it more effectively.

Aminoglycoside Antibiotics

Aminoglycoside Antibiotics Book
Author : Dev P. Arya
Publisher : John Wiley & Sons
Release : 2007-06-29
ISBN : 047174302X
Language : En, Es, Fr & De

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Book Description :

Advances that open new avenues in developing aminoglycoside antibiotics During the last twenty years, there have been numerous advances in the understanding of the chemistry, biochemistry, and recognition of aminoglycosides. This has led to the development of novel antibiotics and opened up new therapeutic targets for intervention. This is the first book to provide a complete overview of recent advances in the field and explore their tremendous potential for drug discovery and rational drug design. With chapters written by one or more leading experts in their specialty areas, the book addresses the chemistry, biology, and toxicology of aminoglycosides. Aminoglycoside Antibiotics: From Chemical Biology to Drug Discovery is a great resource for academic and industrial researchers in drug design and mechanism studies and for researchers studying antibiotic resistance, antibiotic design and synthesis, and the discovery of novel pharmaceuticals. It is also a valuable reference for graduate students in pharmacy, pharmaceutical science, biophysics, medicinal chemistry, and chemical biology.

Untangling the Double Helix

Untangling the Double Helix Book
Author : James C. Wang
Publisher : Unknown
Release : 2009
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

The problem of unraveling two intertwined strands during the duplication of DNA was recognized shortly after the proposal of the DNA double helix structure in 1953. A group of enzymes called DNA topoisomerases solve this problem by breaking and rejoining DNA molecules in a controlled manner, thereby allowing strands to be passed through each other and thus untangled—not just during DNA replication, but also during many other basic cellular processes. Because of their intimate involvement in the workings of the cell, topoisomerases are also the logical targets of many antibiotics (including Cipro) and anticancer agents. This book, written by James Wang, the discoverer of the first topoisomerase and a leader in the field since, presents ten chapters covering the historical backdrop of the DNA entanglement problem and the discovery of the DNA topoisomerases, how DNA topoisomerases perform their magic in DNA replication, transcription, genetic recombination and chromosome condensation, and how they are targets of therapeutic agents. The book should appeal to readers from undergraduates upwards with interests in the biological and clinical aspects of topoisomerase function, or in the mathematics and physics of topology.

Bioinspired Design of Precision Antimycobacterial Peptides

Bioinspired Design of Precision Antimycobacterial Peptides Book
Author : Agustey Shikhar Mongia
Publisher : Unknown
Release : 2019
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

The rapid and continuous emergence of multidrug resistant bacteria threatens to erase the gains antibiotics have made in modern medicine. Pathogens responsible for human infections, particularly of the respiratory tract (e.g. pneumonia, tuberculosis), are highly adept at mutating to develop drug resistance mechanisms. The development of new antimicrobial tools with unique mechanisms of action combats the growing threat of drug-resistant superinfections. One class of such agents is antimicrobial peptides (AMPs), which potently kill drug-resistant bacteria through physical disruption of their membranes, a mechanism not shared by conventional antibiotics. Importantly, these membrane-active sequences permeabilize bacterial cell walls to enhance diffusion of antibiotics and thereby enhance their potency through synergistic mechanisms. This study focuses on the development of a new AMP with potent and selective action against Mycobacterium tuberculosis (Mtb), the causative agent of Tuberculosis (TB), and exploring its mechanism of action. In addition, this study examines the synergistic activity of the peptide with clinically approved antibiotics against both drug-sensitive and antibiotic-resistant respiratory pathogens. The peptide studied was shown to target Mycobacterium strains, specifically M. tuberculosis and M. smegmatis, as opposed to gram-positive and gram-negative bacteria. Through biophysical assays, it was shown that this peptide is capable of disrupting mycolic acid cord factor lipids, the common virulent factor in Mycobacterium strains. In combination with current clinically approved antibiotics, the peptide showed synergistic and additive effects in both mycobacterial strains. Further studies were completed to test toxicity in macrophages and human controls. These results may enable the development of targeted, narrow-spectrum antimicrobial strategies capable of killing bacterial pathogens, without disrupting commensal microbial communities important for preventing drug-resistance and opportunistic infections.

Discovery and Characterization of the Antibacterial Activity of Small Molecules

Discovery and Characterization of the Antibacterial Activity of Small Molecules Book
Author : Katherine Ann Hurley
Publisher : Unknown
Release : 2016
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

The discovery of antibiotics had an enormous impact on medicine because it revolutionized medical procedures and prolonged the life expectancy of patients. The unrestricted, yet indispensable, use of antibiotics in clinics has led to the accumulation of infections associated with drug resistant strains of bacteria. The majority of the antibiotics that are commonly utilized were discovered during the 'golden age' — the 1940s to 1960s — of antibacterial discovery. Unfortunately, no new classes of antibiotics have been discovered in 29 years. The prevalence of antibiotic resistant bacteria and the lack of discovery have produced a difficult situation that necessitates global attention and collaborative action. In this thesis, we describe our contribution to filling the antibacterial discovery void. We illustrate several discovery strategies used in antibiotic research and explain experimental characterization challenges in the context of identifying inhibitors of the cytoskeletal protein, FtsZ. We describe the mechanism of action and new potent analogs of a new class of narrow spectrum DNA gyrase inhibitors. We characterize a new class of broad-spectrum membrane-targeting small molecules with a unique phenotype using a structure-activity relationship study and cell imaging studies. Finally, we identified another class of membrane-targeting small molecules, which demonstrate potential as antibiotic adjuvants against clinically relevant gram-negative and gram-positive bacteria. These projects have provided promising small molecules with antibacterial activity and therapeutic potential as antibiotics.

Genetic Engineering News

Genetic Engineering News Book
Author : Anonim
Publisher : Unknown
Release : 2005
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Genetic Engineering News book written by , available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.