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Special Issue "Discovery of Enzyme Inhibitors from Natural Products"

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

Deadline for manuscript submissions: 31 December 2021.

Special Issue Editors

Prof. Dr. Fengqing Yang
E-Mail Website
Guest Editor
School of Chemistry and Chemical Engineering, Chongqing University, Chongqing, China
Interests: natural products; drug discovery; enzyme inhibitors; antithrombosis; pharmaceutical analysis
Prof. Dr. Jianbo Wan
E-Mail Website
Guest Editor
Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China
Interests: metabolic syndrome; alcoholic liver disease; nonalcoholic liver disease; atherosclerosis; metabolomics; LC-MS
Dr. Liya Ge
E-Mail Website
Guest Editor
Nanyang Environment and Water Research Institute, Nanyang Technological University, Singapore 637141, Singapore
Interests: analytical & bioanalytical chemistry; polymer chemistry & polymer chemical engineering

Special Issue Information

Dear Colleagues,

Enzymes have high catalytic activity, substrate specificity and good biodegradability, which can selectively catalyze a series of biochemical reactions. Inhibition of enzyme activity is considered as a promising approach for treating human diseases. For example, thrombin plays an important role in the processes of thrombosis, and its inhibitors can be used for the treatment of cardiovascular diseases. Glycosidase inhibitors have the potential to be used as drugs for the treatment of diabetes, viral infections, cancers and hereditary lysosomal storage diseases. The inhibition of excessive trypsin activity can be considered as a treatment method for diseases, such as severe acute pancreatitis, fibrosis, hypertension, rheumatoid arthritis and diabetes. Reducing the conversion of xanthine to uric acid by inhibiting the xanthine oxidase activity has become the main approach for the treatment of gout. Tyrosinase inhibitors are potential medicines for the prevention of melanoma and skin tumors.

Natural products are rich sources of new drug discovery, due to their structural diversity. We would like to invite authors to contribute original research and review articles that will stimulate the basic research on the discovery of enzyme inhibitors from natural products. In this Special Issue, we will pay special attention to the manuscripts that evaluate and discuss the screening methods, action mechanisms or expert consensus of natural product-derived enzyme inhibitors. Potential topics suitable for this Special Issue include, but are not limited to:

  • Recent advances of discovery of enzyme inhibitors from natural products;
  • The use of natural products in the treatment of diseases based on enzyme targets;
  • The state-of-the-art technology to discover enzyme inhibitors from natural products;
  • SAR studies (structure/activity relationship) of enzyme-targeted natural compounds;
  • Natural substances as lead compounds for new drugs in enzyme targeting therapy.

Prof. Dr. Fengqing Yang
Prof. Dr. Jianbo Wan
Dr. Liya Ge
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • enzyme inhibitor
  • natural product
  • drug discovery

Published Papers (5 papers)

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Research

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Article
Personal Glucose Meter for α-Glucosidase Inhibitor Screening Based on the Hydrolysis of Maltose
Molecules 2021, 26(15), 4638; https://doi.org/10.3390/molecules26154638 - 30 Jul 2021
Cited by 1 | Viewed by 553
Abstract
As a key enzyme regulating postprandial blood glucose, α-Glucosidase is considered to be an effective target for the treatment of diabetes mellitus. In this study, a simple, rapid, and effective method for enzyme inhibitors screening assay was established based on α-glucosidase catalyzes reactions [...] Read more.
As a key enzyme regulating postprandial blood glucose, α-Glucosidase is considered to be an effective target for the treatment of diabetes mellitus. In this study, a simple, rapid, and effective method for enzyme inhibitors screening assay was established based on α-glucosidase catalyzes reactions in a personal glucose meter (PGM). α-glucosidase catalyzes the hydrolysis of maltose to produce glucose, which triggers the reduction of ferricyanide (K3[Fe(CN)6]) to ferrocyanide (K4[Fe(CN)6]) and generates the PGM detectable signals. When the α-glucosidase inhibitor (such as acarbose) is added, the yield of glucose and the readout of PGM decreased accordingly. This method can achieve the direct determination of α-glucosidase activity by the PGM as simple as the blood glucose tests. Under the optimal experimental conditions, the developed method was applied to evaluate the inhibitory activity of thirty-four small-molecule compounds and eighteen medicinal plants extracts on α-glucosidase. The results exhibit that lithospermic acid (52.5 ± 3.0%) and protocatechualdehyde (36.8 ± 2.8%) have higher inhibitory activity than that of positive control acarbose (31.5 ± 2.5%) at the same final concentration of 5.0 mM. Besides, the lemon extract has a good inhibitory effect on α-glucosidase with a percentage of inhibition of 43.3 ± 3.5%. Finally, the binding sites and modes of four active small-molecule compounds to α-glucosidase were investigated by molecular docking analysis. These results indicate that the PGM method is feasible to screening inhibitors from natural products with simple and rapid operations. Full article
(This article belongs to the Special Issue Discovery of Enzyme Inhibitors from Natural Products)
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Article
Phytochemical Composition, Antioxidant Activity, and Enzyme Inhibitory Activities (α-Glucosidase, Xanthine Oxidase, and Acetylcholinesterase) of Musella lasiocarpa
Molecules 2021, 26(15), 4472; https://doi.org/10.3390/molecules26154472 - 24 Jul 2021
Viewed by 558
Abstract
In this study, we aimed to investigate the chemical components and biological activities of Musella lasiocarpa, a special flower that is edible and has functional properties. The crude methanol extract and its four fractions (petroleum ether, ethyl acetate, n-butanol, and aqueous fractions) [...] Read more.
In this study, we aimed to investigate the chemical components and biological activities of Musella lasiocarpa, a special flower that is edible and has functional properties. The crude methanol extract and its four fractions (petroleum ether, ethyl acetate, n-butanol, and aqueous fractions) were tested for their total antioxidant capacity, followed by their α-glucosidase, acetylcholinesterase, and xanthine oxidase inhibitory activities. Among the samples, the highest total phenolic and total flavonoid contents were found in the ethyl acetate (EtOAc) fraction (224.99 mg GAE/g DE) and crude methanol extract (187.81 mg QE/g DE), respectively. The EtOAc fraction of Musella lasiocarpa exhibited the strongest DPPH· scavenging ability, ABTS·+ scavenging ability, and α-glucosidase inhibitory activity with the IC50 values of 22.17, 12.10, and 125.66 μg/mL, respectively. The EtOAc fraction also showed the strongest ferric reducing antioxidant power (1513.89 mg FeSO4/g DE) and oxygen radical absorbance capacity ability (524.11 mg Trolox/g DE), which were higher than those of the control BHT. In contrast, the aqueous fraction demonstrated the highest acetylcholinesterase inhibitory activity (IC50 = 10.11 μg/mL), and the best xanthine oxidase inhibitory ability (IC50 = 5.23 μg/mL) was observed from the crude methanol extract as compared with allopurinol (24.85 μg/mL). The HPLC-MS/MS and GC-MS analyses further revealed an impressive arsenal of compounds, including phenolic acids, fatty acids, esters, terpenoids, and flavonoids, in the most biologically active EtOAc fraction. Taken together, this is the first report indicating the potential of Musella lasiocarpa as an excellent natural source of antioxidants with possible therapeutic, nutraceutical, and functional food applications. Full article
(This article belongs to the Special Issue Discovery of Enzyme Inhibitors from Natural Products)
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Article
Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis, In Vitro and In Silico Studies
Molecules 2021, 26(14), 4375; https://doi.org/10.3390/molecules26144375 - 20 Jul 2021
Viewed by 599
Abstract
Regulating insulin and leptin levels using a protein tyrosine phosphatase 1B (PTP1B) inhibitor is an attractive strategy to treat diabetes and obesity. Glycyrrhetinic acid (GA), a triterpenoid, may weakly inhibit this enzyme. Nonetheless, semisynthetic derivatives of GA have not been developed as PTP1B [...] Read more.
Regulating insulin and leptin levels using a protein tyrosine phosphatase 1B (PTP1B) inhibitor is an attractive strategy to treat diabetes and obesity. Glycyrrhetinic acid (GA), a triterpenoid, may weakly inhibit this enzyme. Nonetheless, semisynthetic derivatives of GA have not been developed as PTP1B inhibitors to date. Herein we describe the synthesis and evaluation of two series of indole- and N-phenylpyrazole-GA derivatives (4af and 5af). We measured their inhibitory activity and enzyme kinetics against PTP1B using p-nitrophenylphosphate (pNPP) assay. GA derivatives bearing substituted indoles or N-phenylpyrazoles fused to their A-ring showed a 50% inhibitory concentration for PTP1B in a range from 2.5 to 10.1 µM. The trifluoromethyl derivative of indole-GA (4f) exhibited non-competitive inhibition of PTP1B as well as higher potency (IC50 = 2.5 µM) than that of positive controls ursolic acid (IC50 = 5.6 µM), claramine (IC50 = 13.7 µM) and suramin (IC50 = 4.1 µM). Finally, docking and molecular dynamics simulations provided the theoretical basis for the favorable activity of the designed compounds. Full article
(This article belongs to the Special Issue Discovery of Enzyme Inhibitors from Natural Products)
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Article
Evaluation of Enzyme Inhibitory Activity of Flavonoids by Polydopamine-Modified Hollow Fiber-Immobilized Xanthine Oxidase
Molecules 2021, 26(13), 3931; https://doi.org/10.3390/molecules26133931 - 28 Jun 2021
Viewed by 586
Abstract
In this study, a polydopamine (PDA)-modified hollow fiber-immobilized xanthine oxidase (XOD) was prepared for screening potential XOD inhibitors from flavonoids. Several parameters for the preparation of PDA-modified hollow fiber-immobilized XOD, including the dopamine concentration, modification time, XOD concentration and immobilization time, were optimized. [...] Read more.
In this study, a polydopamine (PDA)-modified hollow fiber-immobilized xanthine oxidase (XOD) was prepared for screening potential XOD inhibitors from flavonoids. Several parameters for the preparation of PDA-modified hollow fiber-immobilized XOD, including the dopamine concentration, modification time, XOD concentration and immobilization time, were optimized. The results show that the optimal conditions for immobilized XOD activity were a dopamine concentration of 2.0 mg/mL in 10.0 mM Tris-HCl buffer (pH 8.5), a modification time of 3.0 h, an XOD concentration of 1000 μg/mL in 10.0 mM phosphate buffer (pH 7.5) and an immobilization time of 3.0 h. Subsequently, the enzymatic reaction conditions such as the pH value and temperature were investigated, and the enzyme kinetics and inhibition parameters were determined. The results indicate that the optimal pH value (7.5) and temperature (37 °C) of the PDA-modified hollow fiber-immobilized XOD were consistent with the free enzyme. Moreover, the PDA-modified hollow fiber-immobilized XOD could still maintain above 50% of its initial immobilized enzyme activity after seven consecutive cycles. The Michaelis–Menten constant (Km) and the half-maximal inhibitory concentration (IC50) of allopurinol on the immobilized XOD were determined as 0.25 mM and 23.2 μM, respectively. Furthermore, the PDA-modified hollow fiber-immobilized XOD was successfully applied to evaluate the inhibitory activity of eight flavonoids. Quercetin, apigenin, puerarin and epigallocatechin showed a good inhibition effect, and their percentages of inhibition were (79.86 ± 3.50)%, (80.98 ± 0.64)%, (61.15 ± 6.26)% and (54.92 ± 0.41)%, respectively. Finally, molecular docking analysis further verified that these four active compounds could bind to the amino acid residues in the XOD active site. In summary, the PDA-modified hollow fiber-immobilized XOD is an efficient method for the primary screening of XOD inhibitors from natural products. Full article
(This article belongs to the Special Issue Discovery of Enzyme Inhibitors from Natural Products)
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Review

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Review
Non-Alkaloid Cholinesterase Inhibitory Compounds from Natural Sources
Molecules 2021, 26(18), 5582; https://doi.org/10.3390/molecules26185582 - 14 Sep 2021
Viewed by 392
Abstract
Alzheimer’s disease (AD) is a severe neurodegenerative disorder of different brain regions accompanied by distresses and affecting more than 25 million people in the world. This progressive brain deterioration affects the central nervous system and has negative impacts on a patient’s daily activities [...] Read more.
Alzheimer’s disease (AD) is a severe neurodegenerative disorder of different brain regions accompanied by distresses and affecting more than 25 million people in the world. This progressive brain deterioration affects the central nervous system and has negative impacts on a patient’s daily activities such as memory impairment. The most important challenge concerning AD is the development of new drugs for long-term treatment or prevention, with lesser side effects and greater efficiency as cholinesterases inhibitors and the ability to remove amyloid-beta(Aβ) deposits and other related AD neuropathologies. Natural sources provide promising alternatives to synthetic cholinesterase inhibitors and many have been reported for alkaloids while neglecting other classes with potential cholinesterase inhibition. This review summarizes information about the therapeutic potential of small natural molecules from medicinal herbs, belonging to terpenoids, coumarins, and phenolic compounds, and others, which have gained special attention due to their specific modes of action and their advantages of low toxicity and high efficiency in the treatment of AD. Some show superior drug-like features in comparison to synthetic cholinesterase inhibitors. We expect that the listed phytoconstituents in this review will serve as promising tools and chemical scaffolds for the discovery of new potent therapeutic leads for the amelioration and treatment of Alzheimer’s disease. Full article
(This article belongs to the Special Issue Discovery of Enzyme Inhibitors from Natural Products)
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