Pseudo-natural products and natural product-inspired methods in chemical biology and drug discovery

Grigalunas, Michael; Burhop, Annina; Christoforow, Andreas; Waldmann, Herbert

doi:10.1016/j.cbpa.2019.10.005

Cited by 64 publications

(67 citation statements)

References 36 publications

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“…Biologically relevant natural products (NPs) generated through evolution have served as inspiration in the design of new bioactive small molecule classes, [1] for example, in the establishment of Biology Oriented Synthesis (BIOS) [2] and the complexity to diversity (CtD) approach [3, 4] . We have recently introduced the design and synthesis of pseudo natural products (pseudo‐NPs) as new strategy for the discovery of novel bioactive chemical matter [5, 6] …”

Section: Introductionmentioning

confidence: 99%

“…[3,4] We have recently introduced the design and synthesis of pseudo natural products (pseudo-NPs) as new strategy for the discovery of novel bioactive chemical matter. [5,6] Pseudo-NPs are synthesized through de novo combinations of NP fragments [7] in unprecedented arrangements. Thereby,t hey go beyond the chemical space explored in NP biosynthesis and may have new biological targets and modes of action.…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis, and Biological Evaluation of Chemically and Biologically Diverse Pyrroquinoline Pseudo Natural Products

et al. 2021

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Natural product (NP) structures are a rich source of inspiration for the discovery of new biologically relevant chemical matter. In natural product inspired pseudo‐NPs, NP‐derived fragments are combined de novo in unprecedented arrangements. Described here is the design and synthesis of a 155‐member pyrroquinoline pseudo‐NP collection in which fragments characteristic of the tetrahydroquinoline and pyrrolidine NP classes are combined with eight different connectivities and regioisomeric arrangements. Cheminformatic analysis and biological evaluation of the compound collection by means of phenotyping in the morphological “cell painting” assay followed by principal component analysis revealed that the pseudo‐NP classes are chemically diverse and that bioactivity patterns differ markedly, and are dependent on connectivity and regioisomeric arrangement of the fragments.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Chemically and Biologically Diverse Pyrroquinoline Pseudo Natural Products

et al. 2021

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“…Herein, we set out to search for new analogs with similar potency and selectivity but an improved pharmacological profile. To this end, we introduced the structural features of the natural product capsaicin ( 2 ), 20 – 22 a well-known TRPV1 ligand also reported as a h TRPV6 modulator. 23 , 24 Our aim was to modify the 3-pyridine and m -phenyl appendages of 1 , which are frequent drug-type substituents and might be responsible for the undesirable off-target effects of 1 .…”

Section: Introductionmentioning

confidence: 99%

Natural product inspired optimization of a selective TRPV6 calcium channel inhibitor

et al. 2020

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“…Natural products are often regarded as evolutionarily optimized ligands for biological targets and receptors [11,12] . For a therapeutic use, however, many natural products need to be improved in terms of selectivity, pharmacokinetic properties, and stability [12–14] .…”

Section: Biotechnological Methods For Natural Product Derivatizationmentioning

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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Pseudo-natural products and natural product-inspired methods in chemical biology and drug discovery

Cited by 64 publications

References 36 publications

Design, Synthesis, and Biological Evaluation of Chemically and Biologically Diverse Pyrroquinoline Pseudo Natural Products

Design, Synthesis, and Biological Evaluation of Chemically and Biologically Diverse Pyrroquinoline Pseudo Natural Products

Natural product inspired optimization of a selective TRPV6 calcium channel inhibitor

Bioengineering of Anti‐Inflammatory Natural Products

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