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Natural Terpenoid Alkaloids Therapeutic Perspectives

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (15 October 2021) | Viewed by 11641

Special Issue Editors


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Guest Editor
1. Department of Pharmacognosy, Faculty of Pharmacy, University of Szeged, H-6720 Szeged, Hungary
2. Institute for Translational Medicine, Faculty of Medicine, University of Pécs, Szigeti út 12, 7624 Pécs, Hungary
Interests: phytochemistry; pharmacognosy; phytotherapy; phytochemical analysis
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
Interests: natural product chemistry on fungi; plants; marine organisms; comparative mass spectrometry-based metabolomics strategies for the investigation of natural products secondary metabolites; functional and healthy food; new drugs development
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Diterpene alkaloids (DA) have been isolated primarily from Ranunculaceae species. To date, several hundred such compounds are known and many of these alkaloids have remarkable biological effects. Several DA-containing plants are known to be toxic plants. However, some of these in low doses or after careful processing have been applied in traditional medicine, especially in Asia.

An inhibitory or agonist effect on different ion channels is closely related to the toxic and pharmacologically useful effects of DAs. In the case of appropriate selective affinity to pharmacological targets, DAs can be used as medicines. Certain compounds form part of evidence-based medicine as antiarrhythmic drugs and several other alkaloids are under investigation for their effects on the central nervous system.

The goal of this Special Issue is to provide an overview of the current research results on DAs, including their isolation, structure elucidation, and semisynthetic modifications, and pharmacological investigations thereof.

Assoc. Prof. Dezső Csupor
Prof. Fang-Rong Chang
Prof. Mohamed El-Shazly
Guest Editors

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Keywords

  • diterpene alkaloid
  • norditerpene alkaloid
  • Ranunculaceae
  • vardiovascular
  • central nervous system

Published Papers (3 papers)

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Research

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18 pages, 4680 KiB  
Article
On the Inhibitability of Natural Products Isolated from Tetradium ruticarpum towards Tyrosine Phosphatase 1B (PTP1B) and α-Glucosidase (3W37): An In Vitro and In Silico Study
by Dao-Cuong To, Thanh Q. Bui, Nguyen Thi Ai Nhung, Quoc-Toan Tran, Thi-Thuy Do, Manh-Hung Tran, Phan-Phuoc Hien, Truong-Nhan Ngu, Phan-Tu Quy, The-Hung Nguyen, Huu-Tho Nguyen, Tien-Dung Nguyen and Phi-Hung Nguyen
Molecules 2021, 26(12), 3691; https://doi.org/10.3390/molecules26123691 - 17 Jun 2021
Cited by 5 | Viewed by 3211
Abstract
Folk experiences suggest natural products in Tetradium ruticarpum can be effective inhibitors towards diabetes-related enzymes. The compounds were experimentally isolated, structurally elucidated, and tested in vitro for their inhibition effects on tyrosine phosphatase 1B (PTP1B) and α-glucosidase (3W37). Density functional theory and molecular [...] Read more.
Folk experiences suggest natural products in Tetradium ruticarpum can be effective inhibitors towards diabetes-related enzymes. The compounds were experimentally isolated, structurally elucidated, and tested in vitro for their inhibition effects on tyrosine phosphatase 1B (PTP1B) and α-glucosidase (3W37). Density functional theory and molecular docking techniques were utilized as computational methods to predict the stability of the ligands and simulate interaction between the studied inhibitory agents and the targeted proteins. Structural elucidation identifies two natural products: 2-heptyl-1-methylquinolin-4-one (1) and 3-[4-(4-methylhydroxy-2-butenyloxy)-phenyl]-2-propenol (2). In vitro study shows that the compounds (1 and 2) possess high potentiality for the inhibition of PTP1B (IC50 values of 24.3 ± 0.8, and 47.7 ± 1.1 μM) and α-glucosidase (IC50 values of 92.1 ± 0.8, and 167.4 ± 0.4 μM). DS values and the number of interactions obtained from docking simulation highly correlate with the experimental results yielded. Furthermore, in-depth analyses of the structure–activity relationship suggest significant contributions of amino acids Arg254 and Arg676 to the conformational distortion of PTP1B and 3W37 structures overall, thus leading to the deterioration of their enzymatic activity observed in assay-based experiments. This study encourages further investigations either to develop appropriate alternatives for diabetes treatment or to verify the role of amino acids Arg254 and Arg676. Full article
(This article belongs to the Special Issue Natural Terpenoid Alkaloids Therapeutic Perspectives)
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17 pages, 2330 KiB  
Article
Optimization of Tabersonine Methoxylation to Increase Vindoline Precursor Synthesis in Yeast Cell Factories
by Pamela Lemos Cruz, Natalja Kulagina, Grégory Guirimand, Johan-Owen De Craene, Sébastien Besseau, Arnaud Lanoue, Audrey Oudin, Nathalie Giglioli-Guivarc’h, Nicolas Papon, Marc Clastre and Vincent Courdavault
Molecules 2021, 26(12), 3596; https://doi.org/10.3390/molecules26123596 - 11 Jun 2021
Cited by 8 | Viewed by 2667
Abstract
Plant specialized metabolites are widely used in the pharmaceutical industry, including the monoterpene indole alkaloids (MIAs) vinblastine and vincristine, which both display anticancer activity. Both compounds can be obtained through the chemical condensation of their precursors vindoline and catharanthine extracted from leaves of [...] Read more.
Plant specialized metabolites are widely used in the pharmaceutical industry, including the monoterpene indole alkaloids (MIAs) vinblastine and vincristine, which both display anticancer activity. Both compounds can be obtained through the chemical condensation of their precursors vindoline and catharanthine extracted from leaves of the Madagascar periwinkle. However, the extensive use of these molecules in chemotherapy increases precursor demand and results in recurrent shortages, explaining why the development of alternative production approaches, such microbial cell factories, is mandatory. In this context, the precursor-directed biosynthesis of vindoline from tabersonine in yeast-expressing heterologous biosynthetic genes is of particular interest but has not reached high production scales to date. To circumvent production bottlenecks, the metabolic flux was channeled towards the MIA of interest by modulating the copy number of the first two genes of the vindoline biosynthetic pathway, namely tabersonine 16-hydroxylase and tabersonine-16-O-methyltransferase. Increasing gene copies resulted in an optimized methoxylation of tabersonine and overcame the competition for tabersonine access with the third enzyme of the pathway, tabersonine 3-oxygenase, which exhibits a high substrate promiscuity. Through this approach, we successfully created a yeast strain that produces the fourth biosynthetic intermediate of vindoline without accumulation of other intermediates or undesired side-products. This optimization will probably pave the way towards the future development of yeast cell factories to produce vindoline at an industrial scale. Full article
(This article belongs to the Special Issue Natural Terpenoid Alkaloids Therapeutic Perspectives)
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Review

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28 pages, 9061 KiB  
Review
Classification, Toxicity and Bioactivity of Natural Diterpenoid Alkaloids
by Amin Mahmood Thawabteh, Alà Thawabteh, Filomena Lelario, Sabino Aurelio Bufo and Laura Scrano
Molecules 2021, 26(13), 4103; https://doi.org/10.3390/molecules26134103 - 05 Jul 2021
Cited by 27 | Viewed by 4716
Abstract
Diterpenoid alkaloids are natural compounds having complex structural features with many stereo-centres originating from the amination of natural tetracyclic diterpenes and produced primarily from plants in the Aconitum, Delphinium, Consolida genera. Corals, Xenia, Okinawan/Clavularia, Alcyonacea (soft corals) and [...] Read more.
Diterpenoid alkaloids are natural compounds having complex structural features with many stereo-centres originating from the amination of natural tetracyclic diterpenes and produced primarily from plants in the Aconitum, Delphinium, Consolida genera. Corals, Xenia, Okinawan/Clavularia, Alcyonacea (soft corals) and marine sponges are rich sources of diterpenoids, despite the difficulty to access them and the lack of availability. Researchers have long been concerned with the potential beneficial or harmful effects of diterpenoid alkaloids due to their structural complexity, which accounts for their use as pharmaceuticals as well as their lousy reputation as toxic substances. Compounds belonging to this unique and fascinating family of natural products exhibit a broad spectrum of biological activities. Some of these compounds are on the list of clinical drugs, while others act as incredibly potent neurotoxins. Despite numerous attempts to prepare synthetic products, this review only introduces the natural diterpenoid alkaloids, describing ‘compounds’ structures and classifications and their toxicity and bioactivity. The purpose of the review is to highlight some existing relationships between the presence of substituents in the structure of such molecules and their recognised bioactivity. Full article
(This article belongs to the Special Issue Natural Terpenoid Alkaloids Therapeutic Perspectives)
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