scholarly journals Cheminformatics Analysis of Natural Product Scaffolds: Comparison of Scaffolds Produced by Animals, Plants, Fungi and Bacteria

2020 ◽  
Author(s):  
Peter Ertl ◽  
Tim Schuhmann
Keyword(s):  
Natural Products ◽  
Natural Selection ◽  
Natural Product ◽  
Selection Process ◽  
Structural Features ◽  
New Drugs ◽  
Large Database ◽  
Biologically Relevant ◽  
Different Types ◽  
Selection Of

AbstractNatural products (NPs) have evolved over a very long natural selection process to form optimal interactions with biologically relevant macromolecules. NPs are therefore an extremely useful source of inspiration for the design of new drugs. In the present study we report the results of a cheminformatics analysis of a large database of NP structures focusing on their scaffolds. First, general differences between NP scaffolds and scaffolds from synthetic molecules are discussed, followed by a comparison of the properties of scaffolds produced by different types of organisms. Scaffolds produced by plants are the most complex and those produced by bacteria differ in many structural features from scaffolds produced by other organisms. The results presented here may be used as a guidance in selection of scaffolds for the design of novel NP-like bioactive structures or NP-inspired libraries.

scholarly journals Natural product fragment combination to performance-diverse pseudo-natural products

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Michael Grigalunas ◽  
Annina Burhop ◽  
Sarah Zinken ◽  
Axel Pahl ◽  
José-Manuel Gally ◽  
...  
Keyword(s):  
Natural Products ◽  
Product Design ◽  
Natural Product ◽  
Chemical Space ◽  
Biological Evaluation ◽  
Product Structure ◽  
Biologically Relevant ◽  
Biologically Relevant Chemical Space

AbstractNatural product structure and fragment-based compound development inspire pseudo-natural product design through different combinations of a given natural product fragment set to compound classes expected to be chemically and biologically diverse. We describe the synthetic combination of the fragment-sized natural products quinine, quinidine, sinomenine, and griseofulvin with chromanone or indole-containing fragments to provide a 244-member pseudo-natural product collection. Cheminformatic analyses reveal that the resulting eight pseudo-natural product classes are chemically diverse and share both drug- and natural product-like properties. Unbiased biological evaluation by cell painting demonstrates that bioactivity of pseudo-natural products, guiding natural products, and fragments differ and that combination of different fragments dominates establishment of unique bioactivity. Identification of phenotypic fragment dominance enables design of compound classes with correctly predicted bioactivity. The results demonstrate that fusion of natural product fragments in different combinations and arrangements can provide chemically and biologically diverse pseudo-natural product classes for wider exploration of biologically relevant chemical space.

scholarly journals Exploring the Exceptional Properties of Streptomyces: A Hands-On Discovery of Natural Products

2019 ◽  
Vol 81 (9) ◽  
pp. 658-664
Author(s):  
María Inés Lapaz ◽  
Estefania Juarez Cisneros ◽  
María Julia Pianzzola ◽  
Isolde M. Francis
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Real Life ◽  
Bacterial Challenge ◽  
Microbial Biodiversity ◽  
Streptomyces Species ◽  
Hands On ◽  
Experimental Process ◽  
Metabolic Properties ◽  
Selection Of

Microbial biodiversity and its rich arsenal of natural products is an important and complex biological concept. We propose the use of Streptomyces, one of the most diverse bacterial genera and a major inhabitant of soil, as a model to explain the relevance and importance of this concept. Students will perform experiments ranging from isolation and selection of Streptomyces species, to performing fungal and bacterial challenge assays to evaluate their biocontrol capacity, to screening for specialized metabolic properties such as the production of lipases, amylases, and cellulases. Accompanied by active discussions on the experimental process and results, and integrated into the general microbiology curriculum, this real-life discovery-based lab exercise engages students in current topics concerning natural product discovery and reinforces their understanding of several important concepts in microbiology and biotechnology.

scholarly journals Effect of single tube sections on the structural safety of Chinese solar greenhouse skeletons

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xingan Liu ◽  
Zhenkun Li ◽  
Lei Zhang ◽  
Yu Liu ◽  
Yiming Li ◽  
...  
Keyword(s):  
Material Selection ◽  
Selection Process ◽  
Load Condition ◽  
Structural Features ◽  
Structural Safety ◽  
Element Analysis ◽  
Cross Sectional ◽  
Single Tube ◽  
The Impact ◽  
Selection Of

AbstractIn recent years, the use of single-tube skeletons for the construction of Chinese solar greenhouses has increased. As a consequence, during the selection of the construction materials, the safety of these structures has become an important issue. The single tube section has various forms, but there is no scientific theory to guide the selection process. To the best of our knowledge, the scientific analysis of the impact of single pipe cross section on the safety of greenhouse skeleton has not been addressed so far. In this context, the finite element analysis software was used to calculate and analyze the stress elements, displacement of round tube, Ω tube, elliptic tube and square tube under the same load conditions. We used the Chinese Standard values as a reference and analyzed structural features of different sizes and thicknesses of the greenhouse steel skeleton sections under non-uniform snow load. The results showed that, under the same load condition, the maximum stress in the four skeleton materials was all located at the connection of the transverse tension bar and the front roof. In addition, under same load condition, the greenhouse skeleton with elliptic tube presented the smallest cross-sectional displacement between the different materials tested. The effect of increasing the size of the greenhouse frame was better than that of increasing the greenhouse material thickness. All this work will provide theoretical guidance to the material selection of this structure.

scholarly journals Type S Non Ribosomal Peptide Synthetases for the rapid generation of tailor-made peptide libraries

2021 ◽  
Author(s):  
Nadya Abbood ◽  
Tien Duy Vo ◽  
Jonas Watzel ◽  
Kenan A. J. Bozhueyuek ◽  
Helge B. Bode
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
De Novo ◽  
Chemical Space ◽  
Biologically Relevant ◽  
Peptide Synthetases ◽  
Medical Needs ◽  
Natural Product Research ◽  
Rapid Generation ◽  
Traditional Natural

Bacterial natural products in general, and non-ribosomally synthesized peptides in particular, are structurally diverse and provide us with a broad range of pharmaceutically relevant bioactivities. Yet, traditional natural product research suffers from rediscovering the same scaffolds and has been stigmatised as inefficient, time-, labour-, and cost-intensive. Combinatorial chemistry, on the other hand, can produce new molecules in greater numbers, cheaper and in less time than traditional natural product discovery, but also fails to meet current medical needs due to the limited biologically relevant chemical space that can be addressed. Consequently, methods for the high throughput generation of new-to-nature natural products would offer a new approach to identifying novel bioactive chemical entities for the hit to lead phase of drug discovery programms. As a follow-up to our previously published proof-of-principle study on generating bipartite type S non-ribosomal peptide synthetases (NRPSs), we now envisaged the de novo generation of non-ribosomal peptides (NRPs) on an unreached scale. Using synthetic zippers, we split NRPS in up to three subunits and rapidly generated different bi- and tripartite NRPS libraries to produce 49 peptides, peptide derivatives, and de novo peptides at good titres up to 145 mgL-1. A further advantage of type S NRPSs not only is the possibility to easily expand the created libraries by re-using previously created type S NRPS, but that functions of individual domains as well as domain-domain interactions can be studied and assigned rapidly.

scholarly journals All-carbon [3 + 2] cycloaddition in natural product synthesis

2020 ◽  
Vol 16 ◽  
pp. 3015-3031
Author(s):  
Zhuo Wang ◽  
Junyang Liu
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Structural Features ◽  
Single Step ◽  
Natural Product Synthesis ◽  
Synthetic Chemistry ◽  
Quaternary Centers ◽  
Chemical Structures ◽  
Quaternary Center ◽  
Medicinal Properties

Many natural products possess interesting medicinal properties that arise from their intriguing chemical structures. The highly-substituted carbocycle is one of the most common structural features in many structurally complicated natural products. However, the construction of highly-substituted, stereo-congested, five-membered carbocycles containing all-carbon quaternary center(s) is, at present, a distinct challenge in modern synthetic chemistry, which can be accessed through the all-carbon [3 + 2] cycloaddition. More importantly, the all-carbon [3 + 2] cycloaddition can forge vicinal all-carbon quaternary centers in a single step and has been demonstrated in the synthesis of complex natural products. In this review, we present the development of all-carbon [3 + 2] cycloadditions and illustrate their application in natural product synthesis reported in the last decade covering 2011–2020 (inclusive).

scholarly journals Structure-Based Identification of Potent Natural Product Chemotypes as Cannabinoid Receptor 1 Inverse Agonists

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2630 ◽  
Author(s):  
Pankaj Pandey ◽  
Kuldeep Roy ◽  
Haining Liu ◽  
Guoyi Ma ◽  
Sara Pettaway ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Binding Affinity ◽  
Cannabinoid Receptor ◽  
New Drugs ◽  
In Vitro Screening ◽  
Cannabinoid Receptor 1 ◽  
Cardiometabolic Disorders ◽  
Cb1 Antagonists

Natural products are an abundant source of potential drugs, and their diversity makes them a rich and viable prospective source of bioactive cannabinoid ligands. Cannabinoid receptor 1 (CB1) antagonists are clinically established and well documented as potential therapeutics for treating obesity, obesity-related cardiometabolic disorders, pain, and drug/substance abuse, but their associated CNS-mediated adverse effects hinder the development of potential new drugs and no such drug is currently on the market. This limitation amplifies the need for new agents with reduced or no CNS-mediated side effects. We are interested in the discovery of new natural product chemotypes as CB1 antagonists, which may serve as good starting points for further optimization towards the development of CB1 therapeutics. In search of new chemotypes as CB1 antagonists, we screened the in silico purchasable natural products subset of the ZINC12 database against our reported CB1 receptor model using the structure-based virtual screening (SBVS) approach. A total of 18 out of 192 top-scoring virtual hits, selected based on structural diversity and key protein–ligand interactions, were purchased and subjected to in vitro screening in competitive radioligand binding assays. The in vitro screening yielded seven compounds exhibiting >50% displacement at 10 μM concentration, and further binding affinity (Ki and IC50) and functional data revealed compound 16 as a potent and selective CB1 inverse agonist (Ki = 121 nM and EC50 = 128 nM) while three other compounds—2, 12, and 18—were potent but nonselective CB1 ligands with low micromolar binding affinity (Ki). In order to explore the structure–activity relationship for compound 16, we further purchased compounds with >80% similarity to compound 16, screened them for CB1 and CB2 activities, and found two potent compounds with sub-micromolar activities. Most importantly, these bioactive compounds represent structurally new natural product chemotypes in the area of cannabinoid research and could be considered for further structural optimization as CB1 ligands.

scholarly journals Selection of Priority Natural Products for Evaluation as Potential Precipitants of Natural Product–Drug Interactions: A NaPDI Center Recommended Approach

2018 ◽  
Vol 46 (7) ◽  
pp. 1046-1052 ◽  
Author(s):  
Emily J. Johnson ◽  
Vanessa González-Peréz ◽  
Dan-Dan Tian ◽  
Yvonne S. Lin ◽  
Jashvant D. Unadkat ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Interactions ◽  
Natural Product ◽  
Selection Of

Bioactive Extracts: Strategies to generate Diversified Natural Product Like Libraries

2022 ◽  
Vol 18 ◽  
Author(s):  
Meenu Aggarwal ◽  
Raman Singh ◽  
Priyanka Ahlawat ◽  
Kuldeep Singh
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Structural Diversity ◽  
New Drugs ◽  
The Novel ◽  
Chemical Derivatization ◽  
Molecular Fragments ◽  
Reverse Phase ◽  
Great Capacity ◽  
Compound Libraries

Abstract: Natural products have stimulated chemists owing to their abundant structural diversity and complexity. Indeed, natural products have performed an essential role, particularly in the cure of cancerous and infectious diseases, thereby posing medicinal researchers with a scope of unexplored chemotypes for the innovation of new drugs. Fusion of chemical derivatization and combinatorial synthesis forms the basis of the concept of chemo diversification of plants. Diverse libraries of natural product analogs are constructed through existing biological and chemical approaches using unique schemes to expand natural product frameworks. This review aims to present several approaches employed to offer innovative opportunities to synthesize NP-inspired compound libraries. Reactive molecular fragments present in most natural products are chemically converted to chemically engineered extracts (CEEs) or semisynthetic compounds constituting distinct libraries. Bio-guided isolation for natural products required vital tools like reverse phase chromatography and bioautographic assays. Different established strategies from DTS, BIOS, CtD, FOS, FBDD to Late-stage diversification facilitate the expansion of molecules with physicochemical properties. In particular, fragment-like natural products with novel skeletons may be used as preliminary points for chemical biology and medicinal chemistry programs with great capacity. In this review, we sum up how NPs have proven fruitful for the novel methodologies responsible for the diversification of complex natural products; thereby, it is worthy of going over the upcoming integration of natural products with combinatorial chemistry.

Opportunities for natural products in 21st century antibiotic discovery

2017 ◽  
Vol 34 (7) ◽  
pp. 694-701 ◽  
Author(s):  
Gerard D. Wright
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
21St Century ◽  
New Drugs ◽  
Natural Product Research ◽  
Antibiotic Discovery

Natural product research is poised to regain prominence in delivering new drugs to solve the antibiotic crisis.

Sign in / Sign up

Export Citation Format

Share Document