Special Issue "New Approaches for the Discovery of Pharmacologically-Active Natural Compounds"

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (1 December 2018).

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Prof. José L. Medina-Franco
E-Mail Website
Guest Editor
DIFACQUIM Research group, Department of Pharmacy, National Autonomous University of Mexico (UNAM), Avenida Universidad 3000, Mexico City 04510, Mexico
Interests: drug discovery; computational medicinal chemistry; chemoinformatics; molecular modeling; epigenetics; natural products; food chemicals

Special Issue Information

Dear Colleagues,

Natural products continue to be a major source of active compounds. Natural products from different sources have provided large number of molecules approved for clinical use or that have been used as starting points of optimization programs. Similarly, natural products have inspired the synthesis and development of biologically active molecules. However, identifying pharmacologically active natural products in an efficient and systematic manner is challenging. To this end, a broad range of experimental and computational approaches have evolved in recent years, boosted by the progress on technological advances of screening strategies. In many cases both experimental and theoretical methods are used in synergy. The goal of this Special Issue is to present recent progress on technological advances and applications of different approaches to identify pharmacologically active natural products.

We invite scientists doing research on this area to submit their original research (as full papers or short communications) and review papers for publication in this Special Issue. Topics of interest include, but are not limited to, metabolomics, high content screening, phenotypic screening, bioprospection of natural products, reverse pharmacognosy, data mining, virtual screening, molecular modelling, and artificial intelligence. Experimental and theoretical research studies are welcome. Multi-disciplinary approaches are encouraged.

I look forward your contributions.

Dr. José L. Medina-Franco
Guest Editor

Manuscript Submission Information

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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. Biomolecules is an international peer-reviewed open access monthly 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 1200 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

  • metabolomics
  • high content screening
  • phenotypic screening
  • bioprospection of natural products
  • reverse pharmacognosy
  • data mining
  • virtual screening
  • molecular modelling
  • artificial intelligence

Published Papers (10 papers)

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Editorial

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Open AccessEditorial
New Approaches for the Discovery of Pharmacologically-Active Natural Compounds
Biomolecules 2019, 9(3), 115; https://doi.org/10.3390/biom9030115 - 23 Mar 2019
Abstract
Natural products continue to be a major source of active compounds [...] Full article

Research

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Open AccessArticle
Analysis of Flavonoids Bioactivity for Cholestatic Liver Disease: Systematic Literature Search and Experimental Approaches
Biomolecules 2019, 9(3), 102; https://doi.org/10.3390/biom9030102 - 14 Mar 2019
Cited by 2
Abstract
Flavonoids are naturally occurring compounds that show health benefits on the liver. However, there is little investigation about identification and evaluation of new flavonoid-containing drugs for cholestatic liver disease, one of the most common liver illnesses. We aimed to a systematic search regarding [...] Read more.
Flavonoids are naturally occurring compounds that show health benefits on the liver. However, there is little investigation about identification and evaluation of new flavonoid-containing drugs for cholestatic liver disease, one of the most common liver illnesses. We aimed to a systematic search regarding efficacy of flavonoids for treatment of cholestatic liver disease, and then evaluate naringenin (NG) as representative flavonoid in an obstructive cholestasis model. We searched for information of experimental and clinical studies in four major databases without time and language limits. Intervention was defined as any flavonoid derivate compared with other flavonoid, placebo, or without comparator. In addition, we evaluated NG on a bile duct-ligated model in order to contribute evidence of its actions. Eleven experimental reports that support the efficacy of flavonoids in cholestatic liver disease were identified. However, there was no homogeneity in efficacy endpoints evaluated and methodology. On the other hand, NG showed beneficial effects by improving specific metabolic (cholesterol and lipoproteins) and liver damage (bilirubin and alkaline phosphatase) biomarkers. The review lacks homogeneous evidence about efficacy of flavonoids in experimental settings, and is susceptible to risk for bias. NG only showed improvements in specific disease biomarkers. More investigation is still needed to determine its potential for drug development. Full article
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Open AccessArticle
NP-Scout: Machine Learning Approach for the Quantification and Visualization of the Natural Product-Likeness of Small Molecules
Biomolecules 2019, 9(2), 43; https://doi.org/10.3390/biom9020043 - 24 Jan 2019
Cited by 7
Abstract
Natural products (NPs) remain the most prolific resource for the development of small-molecule drugs. Here we report a new machine learning approach that allows the identification of natural products with high accuracy. The method also generates similarity maps, which highlight atoms that contribute [...] Read more.
Natural products (NPs) remain the most prolific resource for the development of small-molecule drugs. Here we report a new machine learning approach that allows the identification of natural products with high accuracy. The method also generates similarity maps, which highlight atoms that contribute significantly to the classification of small molecules as a natural product or synthetic molecule. The method can hence be utilized to (i) identify natural products in large molecular libraries, (ii) quantify the natural product-likeness of small molecules, and (iii) visualize atoms in small molecules that are characteristic of natural products or synthetic molecules. The models are based on random forest classifiers trained on data sets consisting of more than 265,000 to 322,000 natural products and synthetic molecules. Two-dimensional molecular descriptors, MACCS keys and Morgan2 fingerprints were explored. On an independent test set the models reached areas under the receiver operating characteristic curve (AUC) of 0.997 and Matthews correlation coefficients (MCCs) of 0.954 and higher. The method was further tested on data from the Dictionary of Natural Products, ChEMBL and other resources. The best-performing models are accessible as a free web service at http://npscout.zbh.uni-hamburg.de/npscout. Full article
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Open AccessArticle
BIOFACQUIM: A Mexican Compound Database of Natural Products
Biomolecules 2019, 9(1), 31; https://doi.org/10.3390/biom9010031 - 17 Jan 2019
Cited by 5
Abstract
Compound databases of natural products have a major impact on drug discovery projects and other areas of research. The number of databases in the public domain with compounds with natural origins is increasing. Several countries, Brazil, France, Panama and, recently, Vietnam, have initiatives [...] Read more.
Compound databases of natural products have a major impact on drug discovery projects and other areas of research. The number of databases in the public domain with compounds with natural origins is increasing. Several countries, Brazil, France, Panama and, recently, Vietnam, have initiatives in place to construct and maintain compound databases that are representative of their diversity. In this proof-of-concept study, we discuss the first version of BIOFACQUIM, a novel compound database with natural products isolated and characterized in Mexico. We discuss its construction, curation, and a complete chemoinformatic characterization of the content and coverage in chemical space. The profile of physicochemical properties, scaffold content, and diversity, as well as structural diversity based on molecular fingerprints is reported. BIOFACQUIM is available for free. Full article
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Open AccessArticle
Squalene Found in Alpine Grassland Soils under a Harsh Environment in the Tibetan Plateau, China
Biomolecules 2018, 8(4), 154; https://doi.org/10.3390/biom8040154 - 20 Nov 2018
Cited by 1
Abstract
Squalene is found in a large number of plants, animals, and microorganisms, as well as other sources, playing an important role as an intermediate in sterol biosynthesis. It is used widely in the food, cosmetics, and medicine industries because of its antioxidant, antistatic, [...] Read more.
Squalene is found in a large number of plants, animals, and microorganisms, as well as other sources, playing an important role as an intermediate in sterol biosynthesis. It is used widely in the food, cosmetics, and medicine industries because of its antioxidant, antistatic, and anti-carcinogenic properties. A higher natural squalene component of lipids is usually reported as being isolated to organisms living in harsh environments. In the Tibetan Plateau, which is characterized by high altitude, strong solar radiation, drought, low temperatures, and thin air, the squalene component was identified in five alpine grasslands soils using the pyrolysis gas chromatography–mass spectrometry (Py-GC/MS) technique. The relative abundance of squalene ranged from 0.93% to 10.66% in soils from the five alpine grasslands, with the highest value found in alpine desert and the lowest in alpine meadow. Furthermore, the relative abundance of squalene in alpine grassland soils was significantly negatively associated with soil chemical/microbial characteristics. These results indicate that the extreme environmental conditions of the Tibetan Plateau may stimulate the microbial biosynthesis of squalene, and the harsher the environment, the higher the relative abundance of soil squalene. Full article
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Open AccessArticle
Synthesis of a Novel α-Glucosyl Ginsenoside F1 by Cyclodextrin Glucanotransferase and Its In Vitro Cosmetic Applications
Biomolecules 2018, 8(4), 142; https://doi.org/10.3390/biom8040142 - 10 Nov 2018
Cited by 2
Abstract
Ginsenosides from Panax ginseng (Korean ginseng) are unique triterpenoidal saponins that are considered to be responsible for most of the pharmacological activities of P. ginseng. However, the various linkage positions cause different pharmacological activities. In this context, we aimed to synthesize new [...] Read more.
Ginsenosides from Panax ginseng (Korean ginseng) are unique triterpenoidal saponins that are considered to be responsible for most of the pharmacological activities of P. ginseng. However, the various linkage positions cause different pharmacological activities. In this context, we aimed to synthesize new derivatives of ginsenosides with unusual linkages that show enhanced pharmacological activities. Novel α-glycosylated derivatives of ginsenoside F1 were synthesized from transglycosylation reactions of dextrin (sugar donor) and ginsenoside F1 (acceptor) by the successive actions of Toruzyme®3.0L, a cyclodextrin glucanotransferase. One of the resultant products was isolated and identified as (20S)-3β,6α,12β-trihydroxydammar-24ene-(20-O-β-D-glucopyranosyl-(1→2)-α-D-glucopyranoside) by various spectroscopic characterization techniques of fast atom bombardment-mass spectrometry (FAB-MS), infrared spectroscopy (IR), proton-nuclear magnetic resonance (1H-NMR), 13C-NMR, gradient heteronuclear single quantum coherence (gHSQC), and gradient heteronuclear multiple bond coherence (gHMBC). As expected, the novel α-glycosylated ginsenoside F1 (G1-F1) exhibited increased solubility, lower cytotoxicity toward human dermal fibroblast cells (HDF), and higher tyrosinase activity and ultraviolet A (UVA)-induced inhibitory activity against matrix metalloproteinase-1 (MMP-1) than ginsenoside F1. Since F1 has been reported as an antiaging and antioxidant agent, the enhanced efficacies of the novel α-glycosylated ginsenoside F1 suggest that it might be useful in cosmetic applications after screening. Full article
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Open AccessArticle
In Silico Studies on Compounds Derived from Calceolaria: Phenylethanoid Glycosides as Potential Multitarget Inhibitors for the Development of Pesticides
Biomolecules 2018, 8(4), 121; https://doi.org/10.3390/biom8040121 - 23 Oct 2018
Cited by 5
Abstract
An increasing occurrence of resistance in insect pests and high mammal toxicity exhibited by common pesticides increase the need for new alternative molecules. Among these alternatives, bioinsecticides are considered to be environmentally friendly and safer than synthetic insecticides. Particularly, plant extracts have shown [...] Read more.
An increasing occurrence of resistance in insect pests and high mammal toxicity exhibited by common pesticides increase the need for new alternative molecules. Among these alternatives, bioinsecticides are considered to be environmentally friendly and safer than synthetic insecticides. Particularly, plant extracts have shown great potential in laboratory conditions. However, the lack of studies that confirm their mechanisms of action diminishes their potential applications on a large scale. Previously, we have reported the insect growth regulator and insecticidal activities of secondary metabolites isolated from plants of the Calceolaria genus. Herein, we report an in silico study of compounds isolated from Calceolaria against acetylcholinesterase, prophenoloxidase, and ecdysone receptor. The molecular docking results are consistent with the previously reported experimental results, which were obtained during the bioevaluation of Calceolaria extracts. Among the compounds, phenylethanoid glycosides, such as verbascoside, exhibited good theoretical affinity to all the analyzed targets. In light of these results, we developed an index to evaluate potential multitarget insecticides based on docking scores. Full article
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Open AccessArticle
A Marine Diterpenoid Modulates the Proteasome Activity in Murine Macrophages Stimulated with LPS
Biomolecules 2018, 8(4), 109; https://doi.org/10.3390/biom8040109 - 05 Oct 2018
Cited by 1
Abstract
The proteasome is an intracellular complex that degrades damaged or unfolded proteins and participates in the regulation of several processes. The immunoproteasome is a specialized form that is expressed in response to proinflammatory signals and is particularly abundant in immune cells. In a [...] Read more.
The proteasome is an intracellular complex that degrades damaged or unfolded proteins and participates in the regulation of several processes. The immunoproteasome is a specialized form that is expressed in response to proinflammatory signals and is particularly abundant in immune cells. In a previous work, we found an anti-inflammatory effect in a diterpenoid extracted from the octocoral Pseudopterogorgia acerosa, here called compound 1. This compound prevented the degradation of inhibitor κB α (IκBα) and the subsequent activation of nuclear factor κB (NFκB), suggesting that this effect might be due to inhibition of the ubiquitin-proteasome system. Here we show that compound 1 inhibits the proteasomal chymotrypsin-like activity (CTL) of murine macrophages in the presence of lipopolysaccharide (LPS) but not in its absence. This effect might be due to the capacity of this compound to inhibit the activity of purified immunoproteasome. The compound inhibits the cell surface expression of major histocompatibility complex (MHC)-I molecules and the production of proinflammatory cytokines induced by LPS in vitro and in vivo, respectively. Molecular docking simulations predicted that compound 1 selectively binds to the catalytic site of immunoproteasome subunits β1i and β5i, which are responsible for the CTL activity. Taken together these findings suggest that the compound could be a selective inhibitor of the immunoproteasome, and hence could pave the way for its future evaluation as a candidate for the treatment of inflammatory disorders and autoimmune diseases. Full article
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Open AccessFeature PaperArticle
Flavonoids as Putative Epi-Modulators: Insight into Their Binding Mode with BRD4 Bromodomains Using Molecular Docking and Dynamics
Biomolecules 2018, 8(3), 61; https://doi.org/10.3390/biom8030061 - 23 Jul 2018
Cited by 3
Abstract
Flavonoids are widely recognized as natural polydrugs, given their anti-inflammatory, antioxidant, sedative, and antineoplastic activities. Recently, different studies showed that flavonoids have the potential to inhibit bromodomain and extraterminal (BET) bromodomains. Previous reports suggested that flavonoids bind between the Z and A loops [...] Read more.
Flavonoids are widely recognized as natural polydrugs, given their anti-inflammatory, antioxidant, sedative, and antineoplastic activities. Recently, different studies showed that flavonoids have the potential to inhibit bromodomain and extraterminal (BET) bromodomains. Previous reports suggested that flavonoids bind between the Z and A loops of the bromodomain (ZA channel) due to their orientation and interactions with P86, V87, L92, L94, and N140. Herein, a comprehensive characterization of the binding modes of fisetin and the biflavonoid, amentoflavone, is discussed. To this end, both compounds were docked with BET bromodomain 4 (BRD4) using four docking programs. The results were post-processed with protein–ligand interaction fingerprints. To gain further insight into the binding mode of the two natural products, the docking results were further analyzed with molecular dynamics simulations. The results showed that amentoflavone makes numerous contacts in the ZA channel, as previously described for flavonoids and kinase inhibitors. It was also found that amentoflavone can potentially make contacts with non-canonical residues for BET inhibition. Most of these contacts were not observed with fisetin. Based on these results, amentoflavone was experimentally tested for BRD4 inhibition, showing activity in the micromolar range. This work may serve as the basis for scaffold optimization and the further characterization of flavonoids as BET inhibitors. Full article
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Review

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Open AccessReview
Formulations of Curcumin Nanoparticles for Brain Diseases
Biomolecules 2019, 9(2), 56; https://doi.org/10.3390/biom9020056 - 08 Feb 2019
Cited by 8
Abstract
Curcumin is a polyphenol that is obtained from Curcuma longa and used in various areas, such as food and textiles. Curcumin has important anti-inflammatory and antioxidant properties that allow it to be applied as treatment for several emerging pathologies. Remarkably, there are an [...] Read more.
Curcumin is a polyphenol that is obtained from Curcuma longa and used in various areas, such as food and textiles. Curcumin has important anti-inflammatory and antioxidant properties that allow it to be applied as treatment for several emerging pathologies. Remarkably, there are an elevated number of publications deriving from the terms “curcumin” and “curcumin brain diseases”, which highlights the increasing impact of this polyphenol and the high number of study groups investigating their therapeutic actions. However, its lack of solubility in aqueous media, as well as its poor bioavailability in biological systems, represent limiting factors for its successful application. In this review article, the analysis of its chemical composition and the pivotal mechanisms for brain applications are addressed in a global manner. Furthermore, we emphasize the use of nanoparticles with curcumin and the benefits that have been reached as an example of the extensive advances in this area of health. Full article
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