Journal ArticleDOI
Microbial natural products: molecular blueprints for antitumor drugs
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TLDR
This review describes only a handful of exemplary natural products and their derivatives as well as those that have served as elegant blueprints for the development of novel synthetic structures that are either currently in use or in clinical or preclinical trials together with some of their earlier analogs in some cases whose failure to proceed aided in the derivation of later compounds.Abstract:
Microbes from two of the three domains of life, the Prokarya, and Eukarya, continue to serve as rich sources of structurally complex chemical scaffolds that have proven to be essential for the development of anticancer therapeutics. This review describes only a handful of exemplary natural products and their derivatives as well as those that have served as elegant blueprints for the development of novel synthetic structures that are either currently in use or in clinical or preclinical trials together with some of their earlier analogs in some cases whose failure to proceed aided in the derivation of later compounds. In every case, a microbe has been either identified as the producer of secondary metabolites or speculated to be involved in the production via symbiotic associations. Finally, rapidly evolving next-generation sequencing technologies have led to the increasing availability of microbial genomes. Relevant examples of genome mining and genetic manipulation are discussed, demonstrating that we have only barely scratched the surface with regards to harnessing the potential of microbes as sources of new pharmaceutical leads/agents or biological probes.read more
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Journal ArticleDOI
Natural product discovery: past, present, and future
Leonard Katz,Richard H. Baltz +1 more
TL;DR: Advances in bioinformatics, mass spectrometry, proteomics, transcriptomics, metabolomics and gene expression are driving the new field of microbial genome mining for applications in natural product discovery and development.
Journal Article
Rapamycin (AY-22,989), a new antifungal antibiotic. II. Fermentation, isolation and characterization.:II. FERMENTATION, ISOLATION AND CHARACTERIZATION
TL;DR: Rapamycin is a new antifungal antibiotic produced by Streptomyces hygroscopicus and can be classified as a triene, highly active against various Candida species, especially Candida albicans.
Journal ArticleDOI
Metabolite induction via microorganism co-culture: A potential way to enhance chemical diversity for drug discovery
TL;DR: Co-culture studies that aim to increase the diversity of metabolites obtained from microbes, with a special emphasis on the multiple methods of performing co-culture experiments, are focused on.
Journal ArticleDOI
A Review of the Microbial Production of Bioactive Natural Products and Biologics.
Janette V. Pham,Mariamawit A. Yilma,Adriana Feliz,Murtadha T. Majid,Nicholas Maffetone,Jorge R. Walker,Eunji Kim,Hyo Je Cho,Jared M. Reynolds,Myoung Chong Song,Sung Ryeol Park,Sung Ryeol Park,Yeo Joon Yoon +12 more
TL;DR: The structures and diverse biological activities of natural products and recombinant proteins that have been exploited as valuable molecules in medicine, agriculture and insect control are introduced and suggested to inspire the development of new therapeutic agents in academia and industry.
Journal ArticleDOI
Marine-sourced anti-cancer and cancer pain control agents in clinical and late preclinical development.
David J. Newman,Gordon M. Cragg +1 more
TL;DR: This review shows the compounds derived from marine sources that are currently in clinical trials against cancer and the use of marine-derived agents to ameliorate the pain from cancers in humans, and to act as an adjuvant in immunological therapies.
References
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Journal ArticleDOI
Rapid identification of a protein binding partner for the marine natural product kahalalide F by using reverse chemical proteomics.
Andrew M. Piggott,Peter Karuso +1 more
TL;DR: Findings suggest that KF is involved in a hitherto unknown oncosis signaling pathway and that disruption of lysosomes is simply the final step in a series of cascading events.
A focus on the preclinical development and clinical status of the histone deacetylase inhibitor
Simon J. Harrison,Mark Bishton,Susan E. Bates,Steven Grant,Richard Piekarz,Ricky W. Johnstone,Yun Dai,Becki Lee,Maria E Araujo,H. Miles Prince +9 more
TL;DR: The laboratory and clinical development of the Romidepsin compound as a single agent that has more recently been evaluated in combination with other anticancer therapeutics, such as proteasome inhibitors are outlined.
Journal ArticleDOI
Diversity through semisynthesis: the chemistry and biological activity of semisynthetic epothilone derivatives
TL;DR: The current review provides a comprehensive overview on the chemical transformations that have been investigated for the major epothilones A and B as starting materials, and it discusses the biological activity of the resulting products.
Journal ArticleDOI
Regioselective synthesis of folate receptor-targeted agents derived from epothilone analogs and folic acid.
Iontcho Radoslavov Vlahov,Gregory D. Vite,Paul J. Kleindl,Yu Wang,Hari Krishna Santhapuram,Fei You,Stephen J. Howard,Soong-Hoon Kim,Francis F.Y. Lee,Christopher P. Leamon +9 more
TL;DR: These folate receptor (FR) targeting compounds are water soluble and incorporate a hydrophilic peptide-based spacer unit and a reducible self-immolative disulfide- based linker system between the FR-targeting ligand and the parent drug.
Journal ArticleDOI
Structure−Activity Relationship of Kahalalide F Synthetic Analogues
Jimenez Jose Carlos,Angel López-Macià,Carol Gracia,Sonia Varón,Marta Carrascal,Josep Maria Caba,Miriam Royo,Andrés Francesch,Carmen Cuevas,Ernest Giralt,Fernando Albericio +10 more
TL;DR: The solid phase synthesis of 132 novel analogues of kahalalide F revealed that KF is highly sensitive to backbone stereotopical modification but not to side chain size modification, suggesting that this compound has a defined conformational structure.
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