This book offers an integrated review of the most recent trends in natural products drug discovery and key lead candidates that are outstanding for their chemistry and biology as a starting point in novel drug development. The authors focus on different trends that are and will continue to be impacting multiples stages of modern drug discovery from NPs that have not been included in other works. This is complemented with a series of case studies from leading experts from industry and academia on key molecules and derivatives that have been chosen for their novelty in chemistry, biology and clinical applications. The book intends to reflect the current confluence of different disciplines in chemical biology and synthetic chemistry supported by a more profound knowledge of systems biology that ensures the concurrency and synergisms of expertise from different research fields that impact in the discovery of novel molecules. In the first section the chapters reflect recent approaches to exploit the biosynthetic potential of microbial resources (including genome mining, metagenomic and epigenetic approaches), as well as biosynthetic chemistry tools to respond to product supply and novel screening alternatives that have lead to the discovery of novel chemistry. The second part reviews, in the form of case studies, some examples of bioactive molecules in the important therapeutic areas of antiinfectives, oncology and antiparasitics.
สารบัญ
Preface; Introduction; Part one: Semisynthesis/ synthesis de novo of NPs: Semisynthesis approach of Ecteinascidin 743 (ET-743, Yondelis«); Chondramides and Chivosazoles – Two metabolites which interfere with the actin cytoskeleton; Class III lantibiotics – an emerging family of thioether containing peptides Mutant manufacturers; progress in enhancing the neurotrophic effects of natural FKBP ligands; Part two: Engineering NP synthetic pathways and genome mining: biosynthesis of indolocarbazole alkaloids and generation of novel derivatives by combinatorial biosynthesis; new lantibiotics from natural and engineered strains; mining microbial genomes for metabolic products of cryptic pathways; mining cyanobacterial genomes for drug-like and bioactive natural products; pigenetic approaches to natural product synthesis in fungi; Part three: New methodologies and screening technologies for the exploitation of microbial resources: novel approaches for exploiting microbial resources at Fundacion MEDINA; discovery and development of Platensimycin and Platencin; coupling chemical genomics and natural products: the discovery of parnafungins and novel antifungal leads; Part four: Novel microbial natural products and derivatives: Retapamulin-a first-in-class pleuromutilin antibiotic; natural products: new agents against MDR tuberculosis; the contribution of marine chemistry in the field of antimalarial research; epothilones as lead structures for new anticancer drugs; future challenges; Index
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Olga Genilloud obtained her Ph.D. in Chemistry (Biochemistry and Molecular Genetics) in 1988 from the Universidad Complutense de Madrid, Spain. After a short stay at the Microbiology Department at Harvard Medical School in Boston, in 1989 she joined the Centro de Investigacion Basica de Espana (CIBE), at Merck Sharp and Dohme in Spain, where she has led for nineteen years the discovery of bacterial natural products as new leads for drug development. In February 2009 she was appointed Scientific Director of Fundacion MEDINA. She is a member of many different scientific societies and has extensive experience in the coordination and management of international scientific working groups and is actively contributing to different Master and Pre-doctoral teaching programs. M¬ Francisca Vicente has a Ph.D. in Biology and Molecular Genetics (1986, Universidad Autonoma de Madrid) and more than 10 years experience in R&D, managing teams and working in the multidisciplinary environment of multinational pharmacy (Merck Sharp and Dohme, Spain) and other research centres (Institute Pasteur, and Hospital Necker, France). She has been in charge of the design, implementation, and supervision of many R&D projects. She is experienced in identifying and managing the economic resources for developing new scientific and technological projects. She has coordinated and managed national and international research groups. Her teaching experience was gained by giving practical and theoretical classes in different masters and university programs. In February 2009, she joined the Fundacion MEDINA as Area Head of the Screening and Target Validation Department.
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