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Journal ArticleDOI

Microbial natural products: molecular blueprints for antitumor drugs

Lesley-Ann Giddings, +1 more
- 03 Sep 2013 - 
- Vol. 40, Iss: 11, pp 1181-1210
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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.

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Citations
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Journal ArticleDOI

Natural product discovery: past, present, and future

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.
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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.

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.

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.

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

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.
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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.
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Regioselective synthesis of folate receptor-targeted agents derived from epothilone analogs and folic acid.

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.
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Structure−Activity Relationship of Kahalalide F Synthetic Analogues

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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