NMR spectroscopy in drug discovery: Tools for combinatorial chemistry, natural products, and metabolism research

2000 ◽  
pp. 137-211 ◽  
Author(s):  
Paul A. Keifer
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Nmr Spectroscopy ◽  
Combinatorial Chemistry

scholarly journals Sponge Derived Bromotyrosines: Structural Diversity through Natural Combinatorial Chemistry

2015 ◽  
Vol 10 (1) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Hendrik Niemann ◽  
Andreas Marmann ◽  
Wenhan Lin ◽  
Peter Proksch
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Chemical Defense ◽  
Combinatorial Chemistry ◽  
Histone Deacetylases ◽  
Ryanodine Receptors ◽  
Building Blocks ◽  
Dna Methyltransferases ◽  
Diverse Range ◽  
Psammaplin A

Sponge derived bromotyrosines are a multifaceted class of marine bioactive compounds that are important for the chemical defense of sponges but also for drug discovery programs as well as for technical applications in the field of antifouling constituents. These compounds, which are mainly accumulated by Verongid sponges, exhibit a diverse range of bioactivities including antibiotic, cytotoxic and antifouling effects. In spite of the simple biogenetic building blocks, which consist only of brominated tyrosine and tyramine units, an impressive diversity of different compounds is obtained through different linkages between these precursors and through structural modifications of the side chains and/or aromatic rings resembling strategies that are known from combinatorial chemistry. As examples for bioactive, structurally divergent bromotyrosines psammaplin A, Aplysina alkaloids featuring aerothionin, aeroplysinin-1 and the dienone, and the bastadins, including the synthetically derived hemibastadin congeners, have been selected for this review. Whereas all of these natural products are believed to be involved in the chemical defense of sponges, some of them may also be of particular relevance to drug discovery due to their interaction with specific molecular targets in eukaryotic cells. These targets involve important enzymes and receptors, such as histone deacetylases (HDAC) and DNA methyltransferases (DNMT), which are inhibited by psammaplin A, as well as ryanodine receptors that are targeted by bastadine type compounds. The hemibastadins such as the synthetically derived dibromohemibastadin are of particular interest due to their antifouling activity. For the latter, a phenoloxidase which catalyzes the bioglue formation needed for firm attachment of fouling organisms to a given substrate was identified as a molecular target. The Aplysina alkaloids finally provide a vivid example for dynamic wound induced bioconversions of natural products that generate highly efficient chemical weapons precisely when and where needed.

scholarly journals Partitioning Pattern of Natural Products Based on Molecular Properties Descriptors Representing Drug-Likeness

Symmetry ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 546
Author(s):  
Miroslava Nedyalkova ◽  
Vasil Simeonov
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
De Novo ◽  
Target Prediction ◽  
Natural Compounds ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Unique Source ◽  
The Times ◽  
Partitioning Pattern

A cheminformatics procedure for a partitioning model based on 135 natural compounds including Flavonoids, Saponins, Alkaloids, Terpenes and Triterpenes with drug-like features based on a descriptors pool was developed. The knowledge about the applicability of natural products as a unique source for the development of new candidates towards deadly infectious disease is a contemporary challenge for drug discovery. We propose a partitioning scheme for unveiling drug-likeness candidates with properties that are important for a prompt and efficient drug discovery process. In the present study, the vantage point is about the matching of descriptors to build the partitioning model applied to natural compounds with diversity in structures and complexity of action towards the severe diseases, as the actual SARS-CoV-2 virus. In the times of the de novo design techniques, such tools based on a chemometric and symmetrical effect by the implied descriptors represent another noticeable sign for the power and level of the descriptors applicability in drug discovery in establishing activity and target prediction pipeline for unknown drugs properties.

A chemoinformatic analysis of atoms, scaffolds and functional groups in natural products

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Joelle Ngo Hanna ◽  
Boris D. Bekono ◽  
Luc C. O. Owono ◽  
Flavien A. A. Toze ◽  
James A. Mbah ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Physicochemical Properties ◽  
Functional Groups ◽  
Atomic Composition ◽  
Synthetic Compounds ◽  
Chemical Libraries ◽  
Synthetic Drugs ◽  
Drugs Analysis ◽  
Chemical Class

Abstract In the quest to know why natural products (NPs) have often been considered as privileged scaffolds for drug discovery purposes, many investigations into the differences between NPs and synthetic compounds have been carried out. Several attempts to answer this question have led to the investigation of the atomic composition, scaffolds and functional groups (FGs) of NPs, in comparison with synthetic drugs analysis. This chapter briefly describes an atomic enumeration method for chemical libraries that has been applied for the analysis of NP libraries, followed by a description of the main differences between NPs of marine and terrestrial origin in terms of their general physicochemical properties, most common scaffolds and “drug-likeness” properties. The last parts of the work describe an analysis of scaffolds and FGs common in NP libraries, focusing on huge NP databases, e.g. those in the Dictionary of Natural Products (DNP), NPs from cyanobacteria and the largest chemical class of NP – terpenoids.

Recent Advances on Small Molecule Medicinal Chemistry to Treat Human Diseases-Part III

2021 ◽  
Vol 21 (17) ◽  
pp. 1517-1518
Author(s):  
Dharmendra Kumar Yadav
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Small Molecule ◽  
Anticancer Agents ◽  
Medicinal Chemistry ◽  
Review Article ◽  
Human Diseases ◽  
Bioactive Metabolite ◽  
Metabolite Production ◽  
Life Threatening

The discovery and utilization of novel metabolites from natural sources are gaining momentum in the present era. The drug discovery programs have witnessed a remarkable shift from conventional medicines to exploiting natural products and their “value addition”, for treating lifethreatening diseases. The global outbreak of life-threatening diseases namely Ebola, SARS,including infections of the bloodstream (bacteremia), heart valves (endocarditis), lungs (pneumonia), and brain (meningitis) and AIDS calls for a more targeted approach to effectively combat the emerging diseases. In the present scenario, natural products and their extracts are being explored extensively for the treatment of various life threatening diseases. In this thematic issue, several review articles contributed by the scientist and researchers in the different areas of medicinal chemistry, synthetic chemistry, new emerging multi-drug targets were collected. This issue begins with a review article on the “Chemistry and Pharmacology of Natural Catechins from Camellia sinensis as anti-MRSA agents” by Gaur et al. and focuses on the spread of MRSA strains is of great concern because of limited treatment options for staphylococcal infections, since these strains are resistant to the entire class of β-lactam antibiotics. In addition, MRSA exhibits resistance to other classes of antimicrobial agents such as fluoroquinolones, cephalosporins, aminoglycosides, macrolide and even glycopeptides (vancomycin and teicoplanine), leading to the emergence of resistant strains such as glycopeptide intermediate (GISA) and resistant strain (GRSA) of S. aureus. In this review, chemical constituents responsible for the anti-MRSA activity of tea are explored [1]. The next article of this issue is a review article on the “Recent Advancements in the Synthesis and Chemistry of Benzofused Nitrogen- and Oxygen-based Bioactive Heterocycles” by Sharma et al. which focuses on medicinal importance of these bioactive benzo-fused heterocycles; special attention has been given to their synthesis as well as medicinal/pharmaceutical properties in detail [2]. “Trends in pharmaceutical design of Endophytes as anti-infective,” by Tiwari et al., is the third article in this issue. The review focused on the meta-analysis of bioactive metabolite production from endophytes, extensively discussing the bioprospection of natural products for pharmaceutical applications. In light of the emerging importance of endophytes as antiinfective agents, an exploration of the pharmaceutical design of novel chemical entities and analogues has enabled efficient and cost-effective drug discovery programs. However, bottlenecks in endophytic biology and research requires a better understanding of endophytic dynamics and mechanism of bioactive metabolite production towards a sustainable drug discovery program [3]. The last article of this issue is also research article on “Recent development of tetrahydro-quinoline/isoquinoline based compounds as anticancer agents” by Yadav et al. The article reported the synthesis of potent tetrahydroquinoline/isoquinoline molecules of the last 10 years with their anticancer properties in various cancer cell lines and stated their half-maximal inhibitory concentration (IC50). In addition, we also considered the discussion of molecular docking and structural activity relationship wherever provided to understand the possible mode of activity an target involved and structural features responsible for the better activity, so the reader can directly find detail for designing new anticancer agents. [4]. Finally I would like to thank all authors who contributed to this issue, titled “Recent advances on small molecule medicinal chemistry to treat human diseases”.

Combretastatins: From Natural Products to Drug Discovery

ChemInform ◽  
2004 ◽  
Vol 35 (11) ◽  
Author(s):  
Alessandra Cirla ◽  
John Mann
Keyword(s):  
Natural Products ◽  
Drug Discovery
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