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Secondary Metabolites as Therapeutics of Human Pathogens
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Secondary Metabolites as Therapeutics of Human Pathogens

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 7601

Special Issue Editor

Dr. Wieslaw Swietnicki

E-Mail Website
Guest Editor
Łukasiewicz–Industrial Chemistry Institute, Rydygiera 8 Str., 01-793 Warsaw, Poland
Interests: virulence systems; type III secretion system; Yersinia pestis; Pseudomonas aeruginosa; EPEC; inhibitors; vaccines
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Secondary metabolites are compounds produced by organisms for the purpose of signal transduction, the blockage of specific pathways or simply for killing other organisms. The molecules range in size from a few hundred to as much as a few thousand Daltons and are frequently made with the help of non-ribosomal protein synthesis machinery on operons encoding other components, including transport systems, antitoxin components, and gene expression regulators. Secreted components have been used frequently as antibiotics, directly or after synthetic modifications.

This Special Issue will consider manuscripts describing work concentrated in the following areas:

  1. Non-ribosomal protein synthesis proteins: identification, mechanisms of action, structural studies and biological activity against human pathogens;
  2. Experimental identification of compounds with biological activity against human pathogens;
  3. Computational approaches to identifying compounds and predicting their structures;
  4. Genomic regulation of operons producing secondary metabolites and their distribution in other organisms;
  5. Animal models describing the use of secondary metabolites in the therapy of diseases caused by human pathogens;
  6. ADME/toxicology studies and chemical modification of secondary metabolites to improve their application as potential therapeutics.

Dr. Wieslaw Swietnicki
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 submissions that pass pre-check are 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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.

Published Papers (3 papers)

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Research

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15 pages, 4908 KiB  
Article
Neurotrophic and Immunomodulatory Lanostane Triterpenoids from Wood-Inhabiting Basidiomycota
by Khadija Hassan, Blondelle Matio Kemkuignou, Marco Kirchenwitz, Kathrin Wittstein, Monique Rascher-Albaghdadi, Clara Chepkirui, Josphat C. Matasyoh, Cony Decock, Reinhard W. Köster, Theresia E. B. Stradal and Marc Stadler
Int. J. Mol. Sci. 2022, 23(21), 13593; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232113593 - 06 Nov 2022
Cited by 8 | Viewed by 2620
Abstract
Neurotrophins such as nerve growth factor (ngf) and brain-derived neurotrophic factor (bdnf) play important roles in the central nervous system. They are potential therapeutic drugs for the treatment of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. In this study, we investigated the [...] Read more.
Neurotrophins such as nerve growth factor (ngf) and brain-derived neurotrophic factor (bdnf) play important roles in the central nervous system. They are potential therapeutic drugs for the treatment of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. In this study, we investigated the neurotrophic properties of triterpenes isolated from fruiting bodies of Laetiporus sulphureus and a mycelial culture of Antrodia sp. MUCL 56049. The structures of the isolated compounds were elucidated based on nuclear magnetic resonance (NMR) spectroscopy in combination with high-resolution electrospray mass spectrometry (HR-ESIMS). The secondary metabolites were tested for neurotrophin (ngf and bdnf) expression levels on human astrocytoma 1321N1 cells. Neurite outgrowth activity using rat pheochromocytoma (PC-12) cells was also determined. Twelve triterpenoids were isolated, of which several potently stimulated the expression of neurotrophic factors, namely, ngf (sulphurenic acid, 15α-dehydroxytrametenolic acid, fomefficinic acid D, and 16α-hydroxyeburicoic acid) and bdnf (sulphurenic acid and 15α-dehydroxytrametenolic acid), respectively. The triterpenes also potentiated ngf-induced neurite outgrowth in PC-12 cells. This is, to the best of our knowledge, the first report on the compound class of lanostanes in direct relation to bdnf and ngf enhancement. These compounds are widespread in medicinal mushrooms; hence, they appear promising as a starting point for the development of drugs and mycopharmaceuticals to combat neurodegenerative diseases. Interestingly, they do not show any pronounced cytotoxicity and may, therefore, be better suited for therapy than many other neurotrophic compounds that were previously reported. Full article
(This article belongs to the Special Issue Secondary Metabolites as Therapeutics of Human Pathogens)
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15 pages, 37967 KiB  
Article
Functional Insights into Silymarin as an Antiviral Agent against Enterovirus A71 (EV-A71)
by Salima Lalani, Malihe Masomian and Chit Laa Poh
Int. J. Mol. Sci. 2021, 22(16), 8757; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168757 - 15 Aug 2021
Cited by 5 | Viewed by 1934
Abstract
Enterovirus A71 (EV-A71) is a major neurovirulent agent capable of causing severe hand, foot and mouth disease (HFMD) associated with neurological complications and death. Currently, no FDA-approved antiviral is available for the treatment of EV-A71 infections. The flavonoid silymarin was shown to exert [...] Read more.
Enterovirus A71 (EV-A71) is a major neurovirulent agent capable of causing severe hand, foot and mouth disease (HFMD) associated with neurological complications and death. Currently, no FDA-approved antiviral is available for the treatment of EV-A71 infections. The flavonoid silymarin was shown to exert virucidal effects, but the binding site on the capsid was unknown. In this study, the ligand interacting site of silymarin was determined in silico and validated in vitro. Moreover, the potential of EV-A71 to develop resistance against silymarin was further evaluated. Molecular docking of silymarin with the capsid of EV-A71 indicated that silymarin binds to viral protein 1 (VP1) of EV-A71, specifically at the GH loop of VP1. The in vitro binding of silymarin with VP1 of EV-A71 was validated using recombinant VP1 through ELISA competitive binding assay. Continuous passaging of EV-A71 in the presence of silymarin resulted in the emergence of a mutant carrying a substitution of isoleucine by threonine (I97T) at position 97 of the BC loop of EV-A71. The mutation was speculated to overcome the inhibitory effects of silymarin. This study provides functional insights into the underlying mechanism of EV-A71 inhibition by silymarin, but warrants further in vivo evaluation before being developed as a potential therapeutic agent. Full article
(This article belongs to the Special Issue Secondary Metabolites as Therapeutics of Human Pathogens)
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Review

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11 pages, 589 KiB  
Review
The Role of H2S Regulating NLRP3 Inflammasome in Diabetes
by Huijie Zhao, Huiyang Liu, Yihan Yang and Honggang Wang
Int. J. Mol. Sci. 2022, 23(9), 4818; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23094818 - 27 Apr 2022
Cited by 11 | Viewed by 2361
Abstract
Nucleotide-binding oligomeric domain (NOD)-like receptor protein 3 (NLRP3) is a recently discovered cytoplasmic multiprotein complex involved in inflammation. The NLRP3 inflammasome contains NLRP3, apoptosis-related specific protein (ASC) and precursor caspase-1. The NLRP3 inflammasome is involved in many diseases, including diabetes. H2S [...] Read more.
Nucleotide-binding oligomeric domain (NOD)-like receptor protein 3 (NLRP3) is a recently discovered cytoplasmic multiprotein complex involved in inflammation. The NLRP3 inflammasome contains NLRP3, apoptosis-related specific protein (ASC) and precursor caspase-1. The NLRP3 inflammasome is involved in many diseases, including diabetes. H2S is a harmful gas with a rotten egg smell. Recently, it has been identified as the third gas signal molecule after nitric oxide and carbon monoxide. It has many biological functions and plays an important role in many diseases, including diabetes. In recent years, it has been reported that H2S regulation of the NLRP3 inflammasome contributes to a variety of diseases. However, the mechanism has not been fully understood. In this review, we summarized the recent role and mechanism of H2S in regulating the NLRP3 inflammasome in diabetes, in order to provide a theoretical basis for future research. Full article
(This article belongs to the Special Issue Secondary Metabolites as Therapeutics of Human Pathogens)
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