New Aminocoumarin Antibiotics Derived from 4-Hydroxycinnamic Acid are Formed after Heterologous Expression of a Modified Clorobiocin Biosynthetic Gene Cluster

Anderle, Christine; Li, Shu-Ming; Kammerer, Bernd; Gust, Bertolt; Heide, Lutz

doi:10.1038/ja.2007.64

Cited by 18 publications

(7 citation statements)

References 23 publications

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“…Aminocoumarin and their analogues exhibit a wide range of biological applications [9,10]. 3-Aminocoumarin motif can be found in the structures of many antibiotics such as novobiocin, chlorobiocin and coumermycin [11]. A number of articles on 7-aminocoumarins represent photochemical behavior of such compounds that enable these compounds as fluorescent markers [12].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Molecular Docking Studies of (E)-4-(Substituted-benzylideneamino)-2H-Chromen-2-one Derivatives: Entry to New Carbonic Anhydrase Class Of Inhibitors

et al. 2018

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The present article illustrated the synthesis and characterization of a novel series of (E)-4-(substituted-benzylideneamino)-2H-chromen-2-one derivatives 4A-4J: in good to excellent yields. The target compounds were synthesized by refluxing 4-aminocoumarin with aromatic aldehydes in ethanol. The structural confirmation was achieved by spectroscopic techniques such as (H, C-NMR and FT-IR) and elemental analysis. The synthesized compounds were evaluated for carbonic anhydrase II (CA-II) inhibition and free radical scavenging activity. All the compounds showed CA-II inhibition in the micro molar range. The compound 4C: exhibited higher potential in the series with IC=0.0928±0.00545 µM (standard Acetazolamide IC=0.997±0.0586 µM). Pharmacological investigations showed that the synthesized compounds 4A-4J: obey Lipinsk's rule. Compound 4C: elicited drug likeness and showed drug score value of 0.05. Molecular docking analysis showed that compound 4C: interacts with Asn66 and Gln91 amino acid residues. Graphical Abstract.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Molecular Docking Studies of (E)-4-(Substituted-benzylideneamino)-2H-Chromen-2-one Derivatives: Entry to New Carbonic Anhydrase Class Of Inhibitors

et al. 2018

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“…Two other coupled unsaturated protons H‐3 and H‐4 with a coupling constant of J = 4.1 Hz are involved in the aromatic pyrrole. The combined 2D NMR and the literature identify the 5‐methylpyrrole‐2‐carbonyl moiety from C‐1 to C‐6 . The remaining oxygen supports evidence for the C‐8/C‐9 epoxide, as the only available valencies, resulting in the new structure 46 (Table and Fig.…”

Section: Resultsmentioning

confidence: 64%

Miniaturized Cultivation of Microbiota for Antimalarial Drug Discovery

Waterman

Calcul

Beau

et al. 2014

Medicinal Research Reviews

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The ongoing search for effective antiplasmodial agents remains essential in the fight against malaria worldwide. Emerging parasitic drug resistance places an urgent need to explore chemotherapies with novel structures and mechanisms of action. Natural products have historically provided effective antimalarial drug scaffolds. In an effort to search nature's chemical potential for antiplasmodial agents, unconventionally sourced organisms coupled with innovative cultivation techniques were utilized. Approximately 60,000 niche microbes from various habitats (slow-growing terrestrial fungi, Antarctic microbes, and mangrove endophytes) were cultivated on a small-scale, extracted, and used in high-throughput screening to determine antimalarial activity. About 1% of crude extracts were considered active and 6% partially active (≥ 67% inhibition at 5 and 50 μg/mL, respectively). Active extracts (685) were cultivated on a large-scale, fractionated, and screened for both antimalarial activity and cytotoxicity. High interest fractions (397) with an IC50 < 1.11 μg/mL were identified and subjected to chromatographic separation for compound characterization and dereplication. Identifying active compounds with nanomolar antimalarial activity coupled with a selectivity index tenfold higher was accomplished with two of the 52 compounds isolated. This microscale, high-throughput screening project for antiplasmodial agents is discussed in the context of current natural product drug discovery efforts.

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“… 2008 ; Heide 2009 , 2014 ) and to a limited extent with simocyclinones (Anderle et al . 2007a , b ), has raised the possibility of compounds with increased antibacterial potency. However, given that SD8 has been shown to inhibit human topo II (Flatman et al .…”

Section: Simocyclinones As Antibioticsmentioning

confidence: 99%

Structural insights into simocyclinone as an antibiotic, effector ligand and substrate

Buttner

Schäfer

Lawson

et al. 2017

FEMS Microbiology Reviews

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Simocyclinones are antibiotics produced by Streptomyces and Kitasatospora species that inhibit the validated drug target DNA gyrase in a unique way, and they are thus of therapeutic interest. Structural approaches have revealed their mode of action, the inducible-efflux mechanism in the producing organism, and given insight into one step in their biosynthesis. The crystal structures of simocyclinones bound to their target (gyrase), the transcriptional repressor SimR and the biosynthetic enzyme SimC7 reveal fascinating insight into how molecular recognition is achieved with these three unrelated proteins.

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New Aminocoumarin Antibiotics Derived from 4-Hydroxycinnamic Acid are Formed after Heterologous Expression of a Modified Clorobiocin Biosynthetic Gene Cluster

Cited by 18 publications

References 23 publications

Synthesis and Molecular Docking Studies of (E)-4-(Substituted-benzylideneamino)-2H-Chromen-2-one Derivatives: Entry to New Carbonic Anhydrase Class Of Inhibitors

Synthesis and Molecular Docking Studies of (E)-4-(Substituted-benzylideneamino)-2H-Chromen-2-one Derivatives: Entry to New Carbonic Anhydrase Class Of Inhibitors

Miniaturized Cultivation of Microbiota for Antimalarial Drug Discovery

Structural insights into simocyclinone as an antibiotic, effector ligand and substrate

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