Synthesis of natural-product-based compound libraries

2000 ◽  
Vol 4 (3) ◽  
pp. 303-309 ◽  
Author(s):  
Ludger A Wessjohann
Marine Drugs ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 149 ◽  
Author(s):  
Yan Xie ◽  
Yunjiang Feng ◽  
Angela Di Capua ◽  
Tin Mak ◽  
Garry W. Buchko ◽  
...  

In recent years, there has been a revival of interest in phenotypic-based drug discovery (PDD) due to target-based drug discovery (TDD) falling below expectations. Both PDD and TDD have their unique advantages and should be used as complementary methods in drug discovery. The PhenoTarget approach combines the strengths of the PDD and TDD approaches. Phenotypic screening is conducted initially to detect cellular active components and the hits are then screened against a panel of putative targets. This PhenoTarget protocol can be equally applied to pure compound libraries as well as natural product fractions. Here we described the use of the PhenoTarget approach to identify an anti-tuberculosis lead compound. Fractions from Polycarpa aurata were identified with activity against Mycobacterium tuberculosis H37Rv. Native magnetic resonance mass spectrometry (MRMS) against a panel of 37 proteins from Mycobacterium proteomes showed that a fraction from a 95% ethanol re-extraction specifically formed a protein-ligand complex with Rv1466, a putative uncharacterized Mycobacterium tuberculosis protein. The natural product responsible was isolated and characterized to be polycarpine. The molecular weight of the ligand bound to Rv1466, 233 Da, was half the molecular weight of polycarpine less one proton, indicating that polycarpine formed a covalent bond with Rv1466.


2001 ◽  
Vol 6 (16) ◽  
pp. 840-847 ◽  
Author(s):  
Kai U. Bindseil ◽  
Jasmin Jakupovic ◽  
Dietmar Wolf ◽  
Jacques Lavayre ◽  
Jean Leboul ◽  
...  

2018 ◽  
Vol 72 ◽  
pp. 136-149 ◽  
Author(s):  
Pascal Amoa Onguéné ◽  
Conrad V. Simoben ◽  
Ghislain W. Fotso ◽  
Kerstin Andrae-Marobela ◽  
Sami A. Khalid ◽  
...  

2022 ◽  
Vol 18 ◽  
Author(s):  
Meenu Aggarwal ◽  
Raman Singh ◽  
Priyanka Ahlawat ◽  
Kuldeep Singh

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.


2020 ◽  
Vol 37 (11) ◽  
pp. 1497-1510 ◽  
Author(s):  
Gregor S. Cremosnik ◽  
Jie Liu ◽  
Herbert Waldmann

This review provides an overview and historical context to two concepts for the design of natural product-inspired compound libraries and highlights the used synthetic methodologies.


2014 ◽  
Vol 22 (5) ◽  
pp. 1690-1699 ◽  
Author(s):  
Lauren Dyson ◽  
Anthony D. Wright ◽  
Kelly A. Young ◽  
Jennette A. Sakoff ◽  
Adam McCluskey

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