ChemInform Abstract: From Protein Domains to Drug Candidates - Natural Products as Guiding Principles in the Design and Synthesis of Compound Libraries.
Natural products and semi-synthetic compounds continue to be a significant source of drug candidates for a broad range of diseases, including coronavirus disease 2019 (COVID-19), which is causing the current pandemic. Besides being attractive sources of bioactive compounds for further development or optimization, natural products are excellent substrates of unique substructures for fragment-based drug discovery. To this end, fragment libraries should be incorporated into automated drug design pipelines. However, public fragment libraries based on extensive collections of natural products are still limited. Herein, we report the generation and analysis of a fragment library of natural products derived from a database with more than 400,000 compounds. We also report fragment libraries of a large food chemical database and other compound datasets of interest in drug discovery, including compound libraries relevant for COVID-19 drug discovery. The fragment libraries were characterized in terms of content and diversity.
Due to the importance of nature as a source of new drug candidates, the purpose
of this article is to emphasize the marine natural products, which exhibit antitubercular activity,
published between January 2000 and May 2016, with 138 quotations to 250 compounds
obtained from marine resources. These metabolites are organized by chemical constitution
and named as simple alkyl lipids derivatives, aromatics derivatives, peptides, alkaloids,
terpenoids, steroids, macrolides, and polycyclic polyketides.
Background:
In recent years, there has been an improvement in the in vitro and in vivo
methodology for the screening of anti-chagasic compounds. Millions of compounds can now have
their activity evaluated (in large compound libraries) by means of high throughput in vitro
screening assays.
Objective:
Current approaches to drug discovery for Chagas disease.
Method:
This review article examines the contribution of these methodological advances in
medicinal chemistry in the last four years, focusing on Trypanosoma cruzi infection, obtained from
the PubMed, Web of Science, and Scopus databases.
Results:
Here, we have shown that the promise is increasing each year for more lead compounds
for the development of a new drug against Chagas disease.
Conclusion:
There is increased optimism among those working with the objective to find new drug
candidates for optimal treatments against Chagas disease.
The 1,3-butadiene motif is widely found in many natural products and drug candidates with relevant biological activities. Moreover, dienes are important targets for synthetic chemists, due to their ability to give access to a wide range of functional group transformations, including a broad range of C-C bond-forming processes. Therefore, the stereoselective preparation of dienes have attracted much attention over the past decades, and the search for new synthetic protocols continues unabated. The aim of this review is to give an overview of the diverse methodologies that have emerged in the last decade, with a focus on the synthetic processes that meet the requirements of efficiency and sustainability of modern organic chemistry.
AbstractThe spirocyclic motif is abundant in natural products and provides an ideal three-dimensional template to interact with biological targets. With significant attention historically expended on the synthesis of flat-heterocyclic compound libraries, methods to access the less-explored three-dimensional medicinal-chemical space will continue to increase in demand. Herein, we highlight by reaction class the common strategies used to construct the spirocyclic centres embedded in a series of well-studied natural products.1 Introduction2 Cycloadditions3 Palladium-Catalysed Coupling Reactions4 Conjugate Additions5 Imines, Aminals, and Hemiaminal Ethers6 Mannich-Type Reactions7 Oxidative Dearomatisation8 Alkylation9 Organometallic Additions10 Conclusions
Fragment Library of Natural Products and Compound Databases for Drug Discovery