Myxochelin‐Inspired 5‐Lipoxygenase Inhibitors: Synthesis and Biological Evaluation

Schieferdecker, Sebastian; König, Stefanie; Werz, Oliver; Nett, Markus

doi:10.1002/cmdc.201600536

Cited by 11 publications

(17 citation statements)

References 16 publications

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“…Myxochelin, a secondary metabolite obtained from different Myxobacterial strains, responsible for iron uptake during iron-limiting circumstances, was found to be a potent antitumor agent [ 87 , 150 , 151 ]. The ability of nannochelins and hylachelins (siderophores of Myxobacterial source) in inhibiting the human 5-lipoxygenase (5-LO, a gene associated with the proliferation of cancerous cells) were found exerting antitumor activity [ 87 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 ]. It is believed that a similar pathway of inhibiting 5-LO is associated with the strong anticancer activity of myxochelin [ 153 , 155 ].…”

Section: Pharmacological Effects Of Myxobacteria-derived Bioactive Compoundsmentioning

confidence: 99%

Myxobacteria as a Source of New Bioactive Compounds: A Perspective Study

et al. 2021

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Myxobacteria are unicellular, Gram-negative, soil-dwelling, gliding bacteria that belong to class δ-proteobacteria and order Myxococcales. They grow and proliferate by transverse fission under normal conditions, but form fruiting bodies which contain myxospores during unfavorable conditions. In view of the escalating problem of antibiotic resistance among disease-causing pathogens, it becomes mandatory to search for new antibiotics effective against such pathogens from natural sources. Among the different approaches, Myxobacteria, having a rich armor of secondary metabolites, preferably derivatives of polyketide synthases (PKSs) along with non-ribosomal peptide synthases (NRPSs) and their hybrids, are currently being explored as producers of new antibiotics. The Myxobacterial species are functionally characterized to assess their ability to produce antibacterial, antifungal, anticancer, antimalarial, immunosuppressive, cytotoxic and antioxidative bioactive compounds. In our study, we have found their compounds to be effective against a wide range of pathogens associated with the concurrence of different infectious diseases.

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Section: Pharmacological Effects Of Myxobacteria-derived Bioactive Compoundsmentioning

confidence: 99%

Myxobacteria as a Source of New Bioactive Compounds: A Perspective Study

et al. 2021

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“…Finally, myxochelin A and derivatives were obtained after reduction of the ethyl ester to the corresponding primary hydroxyl group with lithium borohydride and demethylation of the 2,3-dimethoxybenzamide moiety with boron tribromide [18]. Later, the same group also used this strategy to synthesize a large set of myxochelin analogues to explore structure-activity relationship with 5-lipoxygenase, an enzyme associated with various types of cancer [19].…”

Section: Total Synthesismentioning

confidence: 99%

Expanding the Myxochelin Natural Product Family by Nicotinic Acid Containing Congeners

Frank

Széles

Akoné

et al. 2021

Preprint

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Myxobacteria represent a viable source of chemically diverse and biologically active secondary metabolites. The myxochelins are a well-studied family of catecholate-type siderophores produced by various myxobacterial strains. Here, we report the discovery, isolation and structure elucidation of three new myxochelins N1–N3 from the terrestrial myxobacterium Corallococcus sp. MCy9049, featuring an unusual nicotinic acid moiety. Precursor-directed biosynthesis (PDB) experiments and total synthesis were performed in order to confirm structures, improve access to pure compounds for bioactivity testing and to devise a biosynthesis proposal. The combined evaluation of metabolome and genome data covering myxobacteria supports the notion that the new myxochelin congeners reported here are in fact frequent side products of the known myxochelin A biosynthetic pathway in myxobacteria.

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“…[79] Due to their comparatively low structural complexity, the myxochelins can be efficiently prepared by total synthesis, [80][81][82] which already enabled an extensive testing of analogues with regard to their 5-LOX inhibitory properties. [83] Noteworthy, several derivatives were also produced by biosynthetic engineering, as this approach omitted the repeated use of identical linear transformations. The corresponding studies initially focused on the two 2,3-dihydroxybenzoate-derived catechol units, which seemed particularly promising residues for a replacement.…”

Section: Myxochelinsmentioning

confidence: 99%

Bioengineering of Anti‐Inflammatory Natural Products

2020

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Inflammatory processes occur as a generic response of the immune system and can be triggered by various factors, such as infection with pathogenic microorganisms or damaged tissue. Due to the complexity of the inflammation process and its role in common diseases like asthma, cancer, skin disorders or Alzheimer's disease, anti‐inflammatory drugs are of high pharmaceutical interest. Nature is a rich source for compounds with anti‐inflammatory properties. Several studies have focused on the structural optimization of natural products to improve their pharmacological properties. As derivatization through total synthesis is often laborious with low yields and limited stereoselectivity, the use of biosynthetic, enzyme‐driven reactions is an attractive alternative for synthesizing and modifying complex bioactive molecules. In this minireview, we present an outline of the biotechnological methods used to derivatize anti‐inflammatory natural products, including precursor‐directed biosynthesis, mutasynthesis, combinatorial biosynthesis, as well as whole‐cell and in vitro biotransformation.

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Myxochelin‐Inspired 5‐Lipoxygenase Inhibitors: Synthesis and Biological Evaluation

Cited by 11 publications

References 16 publications

Myxobacteria as a Source of New Bioactive Compounds: A Perspective Study

Myxobacteria as a Source of New Bioactive Compounds: A Perspective Study

Expanding the Myxochelin Natural Product Family by Nicotinic Acid Containing Congeners

Bioengineering of Anti‐Inflammatory Natural Products

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