Sources of novel antibiotics—aside the common roads (original) (raw)
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Antibiotic discovery in the twenty-first century: current trends and future perspectives
The Journal of …, 2010
New antibiotics are necessary to treat microbial pathogens that are becoming increasingly resistant to available treatment. Despite the medical need, the number of newly approved drugs continues to decline. We offer an overview of the pipeline for new antibiotics at different stages, from compounds in clinical development to newly discovered chemical classes. Consistent with historical data, the majority of antibiotics under clinical development are natural products or derivatives thereof. However, many of them also represent improved variants of marketed compounds, with the consequent risk of being only partially effective against the prevailing resistance mechanisms. In the discovery arena, instead, compounds with promising activities have been obtained from microbial sources and from chemical modification of antibiotic classes other than those in clinical use. Furthermore, new natural product scaffolds have also been discovered by ingenious screening programs. After providing selected examples, we offer our view on the future of antibiotic discovery.
New antibiotic development: barriers and opportunities
Italian Journal of Medicine, 2016
Antibiotic resistance represents a serious threat to public health worldwide, leading to increased healthcare costs, prolonged hospital stays, treatment failures and deaths. To address the emergency of multidrug-resistance, the major international societies of infectious diseases and public health have developed strategies and guidelines to reduce unnecessary antimicrobial use as well as to incite the development of new antibiotics targeting multidrug-resistant pathogens. Even though pharmaceutical companies have been developing new antibiotics since 2010, the global situation is still worrisome. Indeed, the currently available data regarding new antibiotics are limited to microbiological activity and pharmacokinetic profile and their use for the treatment of life-threatening infections (<em>i.e</em>., sepsis) is often off-label. The aim of this article is to present the antibiotic molecules recently commercialized and with which clinicians will deal quite often in next ...
New Antibiotics: Where Are They?
Biomedical Journal of Scientific and Technical Research, 2018
Multidrug resistant bacteria are marching and winning. The entire human race is at risk and new, effective antibiotics are needed for survival. Several notable routines to develop novel antibiotics are briefly compared here and possible new strategies are proposed. Key words include but not limited to nanotechnology, metal nanoparticles, natural product, medicinal plants, folk medicine, ethnopharmacology, computer-based screening, synergistic antibacterial activity, genomics, peptides, inhibitor, and structure-based virtual screening.
Microbial biotechnology, 2016
Due to the threat posed by the increase of highly resistant pathogenic bacteria, there is an urgent need for new antibiotics; all the more so since in the last 20 years, the approval for new antibacterial agents had decreased. The field of natural product discovery has undergone a tremendous development over the past few years. This has been the consequence of several new and revolutionizing drug discovery and development techniques, which is initiating a 'New Age of Antibiotic Discovery'. In this review, we concentrate on the most significant discovery approaches during the last and present years and comment on the challenges facing the community in the coming years.
Discovery and development of new antibiotics: the problem of antibiotic resistance
1993
Real clinical needs for new antimicrobial antibiotics derive from the emergence and dissemination of new opportunistic pathogens, especially in a growing immune system-debilitated host population. The significant health problems that occur as a result of infections with these rare or opportunistic pathogens is an outgrowth of the AIDS epidemic as well as the increasing prevalence of aggressive cancer chemotherapy and organ transplantation. Therapeutic needs can often be met by optimizing the use of existing chemotherapeutic agents. However, commonly prescribed antibiotics may not sufficiently cover these organisms, and the rapid spread or development of antibiotic resistance may compromise standard empiric treatment. Indeed, the greatest threat to successful antibiotic coverage, and hence the driving force behind the search for new therapies, is the evolution and spread of antibiotic resistance. Resistance of common or resurgent pathogens to standard antibiotic therapies is a signif...
Molecules, 2021
The present work aims to examine the worrying problem of antibiotic resistance and the emergence of multidrug-resistant bacterial strains, which have now become really common in hospitals and risk hindering the global control of infectious diseases. After a careful examination of these phenomena and multiple mechanisms that make certain bacteria resistant to specific antibiotics that were originally effective in the treatment of infections caused by the same pathogens, possible strategies to stem antibiotic resistance are analyzed. This paper, therefore, focuses on the most promising new chemical compounds in the current pipeline active against multidrug-resistant organisms that are innovative compared to traditional antibiotics: Firstly, the main antibacterial agents in clinical development (Phase III) from 2017 to 2020 are listed (with special attention on the treatment of infections caused by the pathogens Neisseria gonorrhoeae, including multidrug-resistant isolates, and Clostri...
Pipeline of Known Chemical Classes of Antibiotics
Many approaches are used to discover new antibiotic compounds, one of the most widespread being the chemical modification of known antibiotics. This type of discovery has been so important in the development of new antibiotics that most antibiotics used today belong to the same chemical classes as antibiotics discovered in the 1950s and 1960s. Even though the discovery of new classes of antibiotics is urgently needed, the chemical modification of antibiotics in known classes is still widely used to discover new antibiotics, resulting in a great number of compounds in the discovery and clinical pipeline that belong to existing classes. In this scenario, the present article presents an overview of the R&D pipeline of new antibiotics in known classes of antibiotics, from discovery to clinical trial, in order to map out the technological trends in this type of antibiotic R&D, aiming to identify the chemical classes attracting most interest, their spectrum of activity, and the new subclasses under development. The result of the study shows that the new antibiotics in the pipeline belong to the following chemical classes: quinolones, aminoglycosides, macrolides, oxazolidinones, tetracyclines, pleuromutilins, beta-lactams, lipoglycopeptides, polymyxins and cyclic lipopeptides.
Recent Advances in the Chemistry and Biology of Naturally Occurring Antibiotics
Angewandte Chemie International Edition, 2009
Ever since the world-shaping discovery of penicillin, nature's molecular diversity has been extensively screened for new medications and lead compounds in drug discovery. The search for anti-infective agents intended to combat infectious diseases has been of particular interest and has enjoyed a high degree of success. Indeed, the history of antibiotics is marked with impressive discoveries and drug development stories, the overwhelming majority of which have their origins in nature. Chemistry, and in particular chemical synthesis, has played a major role in bringing naturally occurring antibiotics and their derivatives to the clinic, and no doubt these disciplines will continue to be key enabling technologies for future developments in the field. In this review article, we highlight a number of recent discoveries and advances in the chemistry, biology, and medicine of naturally occurring antibiotics, with particular emphasis on the total synthesis, analog design, and biological evaluation of molecules with novel mechanisms of action.