scholarly journals Shelf-stable electrophilic reagents for the direct incorporation of SCF2CF2H and SCF2CF3 motifs

2021 ◽  
Author(s):  
Jordi Mestre ◽  
Miguel Bernús ◽  
Sergio Castillón ◽  
Omar Boutureira
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Bioactive Compounds ◽  
Electrophilic Reagents ◽  
Scale Preparation ◽  
Shelf Stable ◽  
Direct Incorporation

The introduction of fluoroalkylthioether groups has attracted the attention of the drug discovery community given the special physicochemical and pharmacokinetic features they confer to bioactive compounds. Synthetic advances in the field have been capitalized by methods to incorporate SCF3 and SCF2H motifs, however, longer and synthetically more challenging polyfluoroethyl chains are still underdeveloped. Here, two saccharin-based electrophilic reagents have been disclosed for the efficient incorporation of SCF2CF2H and SCF2CF3 motifs. Their reactivity performance has been thoroughly investigated with a variety of nucleophiles such as thiols, alcohols, amines, alkenes, (hetero)aromatics, and organometallic species, including natural products and pharmaceuticals. Finally, multigram-scale preparation and divergent derivatization has been explored from SCF2CF2H derivatives.

scholarly journals Drug Discovery on Natural Products: From Ion Channels to nAChRs, from Nature to Libraries, from Analytics to Assays

2019 ◽  
Vol 24 (3) ◽  
pp. 362-385 ◽  
Author(s):  
Reka A. Otvos ◽  
Kristina B. M. Still ◽  
Govert W. Somsen ◽  
August B. Smit ◽  
Jeroen Kool
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Ion Channels ◽  
Ion Channel ◽  
Bioactive Compounds ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Drug Targets ◽  
Α7 Nachr ◽  
Analytical Approaches

Natural extracts are complex mixtures that may be rich in useful bioactive compounds and therefore are attractive sources for new leads in drug discovery. This review describes drug discovery from natural products and in explaining this process puts the focus on ion-channel drug discovery. In particular, the identification of bioactives from natural products targeting nicotinic acetylcholine receptors (nAChRs) and serotonin type 3 receptors (5-HT3Rs) is discussed. The review is divided into three parts: “Targets,” “Sources,” and “Approaches.” The “Targets” part will discuss the importance of ion-channel drug targets in general, and the α7-nAChR and 5-HT3Rs in particular. The “Sources” part will discuss the relevance for drug discovery of finding bioactive compounds from various natural sources such as venoms and plant extracts. The “Approaches” part will give an overview of classical and new analytical approaches that are used for the identification of new bioactive compounds with the focus on targeting ion channels. In addition, a selected overview is given of traditional venom-based drug discovery approaches and of diverse hyphenated analytical systems used for screening complex bioactive mixtures including venoms.

Natural Products from Deep-Sea-Derived Fungi ̶ A New Source of Novel Bioactive Compounds?

2018 ◽  
Vol 25 (2) ◽  
pp. 186-207 ◽  
Author(s):  
Georgios Daletos ◽  
Weaam Ebrahim ◽  
Elena Ancheeva ◽  
Mona El-Neketi ◽  
Weiguo Song ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Secondary Metabolites ◽  
Bioactive Compounds ◽  
Deep Sea ◽  
Underlying Assumption ◽  
Pharmacologically Active ◽  
Promising Source ◽  
New Metabolites

Background: Over the last two decades, deep-sea-derived fungi are considered to be a new source of pharmacologically active secondary metabolites for drug discovery mainly based on the underlying assumption that the uniqueness of the deep sea will give rise to equally unprecedented natural products. Indeed, up to now over 200 new metabolites have been identified from deep-sea fungi, which is in support of the statement made above. Results: This review summarizes the new and/or bioactive compounds reported from deepsea- derived fungi in the last six years (2010 – October 2016) and critically evaluates whether the data published so far really support the notion that these fungi are a promising source of new bioactive chemical entities.

Metabolomics: A High-throughput Screen for Biochemical and Bioactivity Diversity in Plants and Crops

2018 ◽  
Vol 24 (19) ◽  
pp. 2043-2054 ◽  
Author(s):  
Alexandre Foito ◽  
Derek Stewart
Keyword(s):  
Mass Spectrometry ◽  
Nuclear Magnetic Resonance ◽  
Natural Products ◽  
Drug Discovery ◽  
Magnetic Resonance ◽  
Bioactive Compounds ◽  
Modern Medicine ◽  
Plant Tissues ◽  
Technical Developments ◽  
Biological Sources

Plants and crops contain a staggering diversity of compounds, many of which have pharmacological activity towards a variety of diseases. These properties have been exploited by traditional and modern medicine providing important sources of healthcare to this day. The contribution of natural products (such as plant-derived) to the modern pharmacopeia is indeed significant; however, the process of identifying novel bioactive compounds from biological sources has been a central challenge in the discovery of natural products. The resolution of these challenges relied extensively on the use of hyphenated Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR)-based analytical technologies for the structural elucidation and annotation of novel compounds. Technical developments in instrumentation and data processing have fostered the development of the field of metabolomics which provides a wealth of tools with the huge potential for application in the process of drug/bioactive discovery from plant tissues. This manuscript provides an overview of the metabolomics toolbox available for the discovery of novel bioactive compounds and the integration of these tools in the bioprospection and drug discovery workflows.

scholarly journals Brine Shrimp Lethality Bioassay: A Tool for Drug Discovery from Natural Products

2020 ◽  
Vol 1 (2) ◽  
pp. 40-48
Author(s):  
George Owusu-Dapaah ◽  
Nicolas I.Y. Fiagbe
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Medicinal Plants ◽  
Bioactive Compounds ◽  
Brine Shrimp ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Brine Shrimp Lethality ◽  
Structure Activity

This study demonstrates the importance of the Brine Shrimp Bioassay in drug discovery. It uses two medicinal plants, Zanthoxylum xanthoxyloides and Tiliacora funifera. Extracts of Zanthoxylum xanthoxyloides were prepared using water, ethanol, chloroform and diethylether, and each subjected to Brine Shrimp Bioassay. The bioactivities of the extracts were found to be in the order diethylether (LD50=0.958 mg/ml), followed by ethanol (LD50=1.874 mg/ml), water(LD50=2.322 mg/ml), and chloroform (3.518 mg/ml). From Tiliacora funifera is isolated the compound funiferine, which is derivatized to obtain o-methylfuniferine and o-isopropylfuniferine. These were subjected to the brine shrimp bioassay, and the structure –activity relationship (SAR) was determined. The results showed that o-isopropylfuniferine is the most bioactive (LD50 = 9.07 mg/ml), followed by o-methylfuniferine (LD50 =38 mg/ml) with funiferine showing the least activity (LD50 =50.25 mg/ml). The SAR of the compounds indicates that the activity of the compounds increases as the size of the group on the phenolic OH is increased, (i.e. isopropyl (C 3 H7 )> methyl (CH3 ) > hydrogen (H)), which suggests that bulkier groups may give more potent compounds. These two results show that the brine shrimp bioassay can be used as a tool in the search for more bioactive compounds from natural products. Keywords: Brine Shrimp Bioassay, Zanthoxylum xanthoxyloides, Funiferine; o-methylfuniferine,o-isopropylfuniferine.

scholarly journals Discovery of Antimalarial Drugs from Streptomycetes Metabolites Using a Metabolomic Approach

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Siti Junaidah Ahmad ◽  
Mohd Badrin Hanizam Abdul Rahim ◽  
Syarul Nataqain Baharum ◽  
Mohd Shukri Baba ◽  
Noraziah Mohamad Zin
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Bioactive Compounds ◽  
Antimalarial Activity ◽  
Classical Method ◽  
Biologically Active ◽  
Gram Positive Bacteria ◽  
H Nmr ◽  
Wide Range ◽  
Bioassay Guided Fractionation

Natural products continue to play an important role as a source of biologically active substances for the development of new drug.Streptomyces, Gram-positive bacteria which are widely distributed in nature, are one of the most popular sources of natural antibiotics. Recently, by using a bioassay-guided fractionation, an antimalarial compound, Gancidin-W, has been discovered from these bacteria. However, this classical method in identifying potentially novel bioactive compounds from the natural products requires considerable effort and is a time-consuming process. Metabolomics is an emerging “omics” technology in systems biology study which integrated in process of discovering drug from natural products. Metabolomics approach in finding novel therapeutics agent for malaria offers dereplication step in screening phase to shorten the process. The highly sensitive instruments, such as Liquid Chromatography-Mass Spectrophotometry (LC-MS), Gas Chromatography-Mass Spectrophotometry (GC-MS), and Nuclear Magnetic Resonance (1H-NMR) spectroscopy, provide a wide range of information in the identification of potentially bioactive compounds. The current paper reviews concepts of metabolomics and its application in drug discovery of malaria treatment as well as assessing the antimalarial activity from natural products. Metabolomics approach in malaria drug discovery is still new and needs to be initiated, especially for drug research in Malaysia.

Fungal Bioactive Compounds in Pharmaceutical Research and Development

2019 ◽  
Vol 15 (2) ◽  
pp. 211-231 ◽  
Author(s):  
Sanjai Saxena ◽  
Manmohan Chhibber ◽  
Inder Pal Singh
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Drug Development ◽  
Natural Product ◽  
Bioactive Compounds ◽  
Medicinal Chemistry ◽  
Bioactive Compound ◽  
New Drugs ◽  
Ecological Groups ◽  
Pharmaceutical Industries

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.

scholarly journals Bacteriophages as tools in drug discovery programs

2010 ◽  
Vol 31 (2) ◽  
pp. 67 ◽  
Author(s):  
Ipek Kurtboke
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Bioactive Compounds ◽  
Bioactive Compound ◽  
Systematic Screening ◽  
Natural Sources ◽  
Microbial Natural Products

Screening of microbial natural products continues to represent an important route to the discovery of novel bioactive compounds for the development of new therapeutic or other important industrial agents. However, a continuous supply of diverse compounds is needed to meet the needs of industry. Such a supply can only be derived through systematic screening of bioactive compound-producing microorganisms from natural sources.

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