scholarly journals Substituents of life: The most common substituent patterns present in natural products

Author(s):  
Peter Ertl

Comparison of substituents present in natural products with the substituents found in average synthetic molecules revealed considerable differences between these 2 groups. The natural products substituents contain mostly oxygen atoms and very little other heteroatoms, are structurally more complex, often containing double bonds and are rich in stereocenters. Substituents found in synthetic molecules contain nitrogen and sulfur atoms, halogenes and more aromatic and particularly heteroaromatic rings. The characteristics of substituents typical for natural products identified here can be useful in the medicinal chemistry context, for example to guide the synthesis of natural product-like libraries and natural product-inspired fragment collections. The results may be used also to support compound derivatization strategies and the design of pseudo-natural natural products.

2019 ◽  
Vol 17 (31) ◽  
pp. 7270-7292 ◽  
Author(s):  
Sagar S. Thorat ◽  
Ravindar Kontham

Oxaspirolactones are ubiquitous structural motifs found in natural products and synthetic molecules with a diverse biochemical and physicochemical profile, and represent a valuable target in natural product chemistry and medicinal chemistry.


ChemInform ◽  
2014 ◽  
Vol 45 (35) ◽  
pp. no-no
Author(s):  
Aman Mahajan ◽  
Renate Hans ◽  
Kelly Chibale ◽  
Vipan Kumar

RSC Advances ◽  
2014 ◽  
Vol 4 (29) ◽  
pp. 15180 ◽  
Author(s):  
Aman Mahajan ◽  
Renate Hans ◽  
Kelly Chibale ◽  
Vipan Kumar

Biomolecules ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 43 ◽  
Author(s):  
Ya Chen ◽  
Conrad Stork ◽  
Steffen Hirte ◽  
Johannes Kirchmair

Natural products (NPs) remain the most prolific resource for the development of small-molecule drugs. Here we report a new machine learning approach that allows the identification of natural products with high accuracy. The method also generates similarity maps, which highlight atoms that contribute significantly to the classification of small molecules as a natural product or synthetic molecule. The method can hence be utilized to (i) identify natural products in large molecular libraries, (ii) quantify the natural product-likeness of small molecules, and (iii) visualize atoms in small molecules that are characteristic of natural products or synthetic molecules. The models are based on random forest classifiers trained on data sets consisting of more than 265,000 to 322,000 natural products and synthetic molecules. Two-dimensional molecular descriptors, MACCS keys and Morgan2 fingerprints were explored. On an independent test set the models reached areas under the receiver operating characteristic curve (AUC) of 0.997 and Matthews correlation coefficients (MCCs) of 0.954 and higher. The method was further tested on data from the Dictionary of Natural Products, ChEMBL and other resources. The best-performing models are accessible as a free web service at http://npscout.zbh.uni-hamburg.de/npscout.


2014 ◽  
Vol 67 (6) ◽  
pp. 827 ◽  
Author(s):  
Andrew M. Beekman ◽  
Russell A. Barrow

Natural products, their derivatives or compounds based on natural product leads constitute ~50 % of clinically used pharmaceuticals. This review highlights pharmaceuticals currently used in Australia and New Zealand that have their origins in fungal metabolites, discussing the natural products chemistry and medicinal chemistry leading to their application as pharmaceuticals.


2019 ◽  
Vol 15 (2) ◽  
pp. 211-231 ◽  
Author(s):  
Sanjai Saxena ◽  
Manmohan Chhibber ◽  
Inder Pal Singh

Background:Exploration of antibiotics from microorganisms became widespread in the academia and the industry with the serendipitous discovery of Penicillin from Penicillium notatum by Sir Alexander Fleming. This embarked the golden era of antibiotics which lasted for over 60 years. However, the traditional phenotypic screening was replaced with more rational and smarter methods of exploration of bioactive compounds from fungi and microorganisms. Fungi have been responsible for providing a variety of bioactive compounds with diverse activities which have been developed into blockbuster drugs such as Cyclosporine, Caspofungin, Lovastatin and Fingolimod etc. It has been reported that ca. 40% of the 1453 New Chemical Entities (NCE’s) approved by USFDA are natural products, natural product inspired or mimics many of which have their origins from fungi. Hence fungal compounds are playing a very important role in drug discovery and development in the pharmaceutical industry.Methods:We undertook structured searches of bibliographic databases of peer-reviewed research literature which pertained to natural products, medicinal chemistry of natural products and drug discovery from fungi. With the strategic improvement in screening and identification methods, fungi are still a potential resource for novel chemistries. Thus the searches also comprised of bioactive agents from fungi isolated or derived from special ecological groups and lineages. To find different molecules derived or isolated from fungi under clinical studies, clinical trial data from the NIH as well as from pharmaceutical companies were also explored. This comprised of data wherein the pharmaceutical industries have acquired or licensed a fungal bioactive compound for clinical study or a trial.Results:Natural product chemistry and medicinal chemistry continue to play an important role in converting a bioactive compound into therapeutic moieties or pharmacophores for new drug development.Conclusion:Thus one can say fungal bioactive compounds are alive and well for development into new drugs as novel ecological groups of fungi as well as novel chemistries are being uncovered. This review further emphasizes the collaboration of fungal biologists with chemists, pharmacologists and biochemists towards the development of newer drugs for taking them into the drug development pipeline.


2018 ◽  
Author(s):  
Jonathan J. Mills ◽  
Kaylib R. Robinson ◽  
Troy E. Zehnder ◽  
Joshua G. Pierce

The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogs to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.


2018 ◽  
Author(s):  
William A. Shirley ◽  
Brian P. Kelley ◽  
Yohann Potier ◽  
John H. Koschwanez ◽  
Robert Bruccoleri ◽  
...  

This pre-print explores ensemble modeling of natural product targets to match chemical structures to precursors found in large open-source gene cluster repository antiSMASH. Commentary on method, effectiveness, and limitations are enclosed. All structures are public domain molecules and have been reviewed for release.


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