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Virtual Screening of Alkaloid and Terpenoid Inhibitors of SMT Expressed in Naegleria sp.
The pathogenic form of thermophilic Naegleria sp. i.e., Naegleria fowleri, also known as brain eating amoeba, causes primary amoebic encephalitis (PAM) with a >97% fatality rate. To date, there are no specific drugs identified to treat this disease specifically. The present antimicrobial combinat...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9457665/ https://www.ncbi.nlm.nih.gov/pubmed/36080504 http://dx.doi.org/10.3390/molecules27175727 |
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author | Abraham, Jason Chauhan, Neha Ray, Supriyo |
author_facet | Abraham, Jason Chauhan, Neha Ray, Supriyo |
author_sort | Abraham, Jason |
collection | PubMed |
description | The pathogenic form of thermophilic Naegleria sp. i.e., Naegleria fowleri, also known as brain eating amoeba, causes primary amoebic encephalitis (PAM) with a >97% fatality rate. To date, there are no specific drugs identified to treat this disease specifically. The present antimicrobial combinatorial chemotherapy is hard on many patients, especially children. Interestingly, Naegleria fowleri has complex lipid biosynthesis pathways like other protists and also has a strong preference to utilize absorbed host lipids for generating energy. The ergosterol biosynthesis pathway provides a unique drug target opportunity, as some of the key enzymes involved in this pathway are absent in humans. Sterol 24-C Methyltransferase (SMT) is one such enzyme that is not found in humans. To select novel inhibitors for this enzyme, alkaloids and terpenoids inhibitors were screened and tested against two isozymes of SMT identified in N. gruberi (non-pathogenic) as well as its homolog found in yeast, i.e., ERG6. Five natural product derived inhibitors i.e., Cyclopamine, Chelerythrine, Berberine, Tanshinone 2A, and Catharanthine have been identified as potential drug candidates based on multiple criteria including binding affinity, ADME scores, absorption, and, most importantly, its ability to cross the blood brain barrier. This study provides multiple leads for future drug exploration against Naegleria fowleri. |
format | Online Article Text |
id | pubmed-9457665 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94576652022-09-09 Virtual Screening of Alkaloid and Terpenoid Inhibitors of SMT Expressed in Naegleria sp. Abraham, Jason Chauhan, Neha Ray, Supriyo Molecules Article The pathogenic form of thermophilic Naegleria sp. i.e., Naegleria fowleri, also known as brain eating amoeba, causes primary amoebic encephalitis (PAM) with a >97% fatality rate. To date, there are no specific drugs identified to treat this disease specifically. The present antimicrobial combinatorial chemotherapy is hard on many patients, especially children. Interestingly, Naegleria fowleri has complex lipid biosynthesis pathways like other protists and also has a strong preference to utilize absorbed host lipids for generating energy. The ergosterol biosynthesis pathway provides a unique drug target opportunity, as some of the key enzymes involved in this pathway are absent in humans. Sterol 24-C Methyltransferase (SMT) is one such enzyme that is not found in humans. To select novel inhibitors for this enzyme, alkaloids and terpenoids inhibitors were screened and tested against two isozymes of SMT identified in N. gruberi (non-pathogenic) as well as its homolog found in yeast, i.e., ERG6. Five natural product derived inhibitors i.e., Cyclopamine, Chelerythrine, Berberine, Tanshinone 2A, and Catharanthine have been identified as potential drug candidates based on multiple criteria including binding affinity, ADME scores, absorption, and, most importantly, its ability to cross the blood brain barrier. This study provides multiple leads for future drug exploration against Naegleria fowleri. MDPI 2022-09-05 /pmc/articles/PMC9457665/ /pubmed/36080504 http://dx.doi.org/10.3390/molecules27175727 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Abraham, Jason Chauhan, Neha Ray, Supriyo Virtual Screening of Alkaloid and Terpenoid Inhibitors of SMT Expressed in Naegleria sp. |
title | Virtual Screening of Alkaloid and Terpenoid Inhibitors of SMT Expressed in Naegleria sp. |
title_full | Virtual Screening of Alkaloid and Terpenoid Inhibitors of SMT Expressed in Naegleria sp. |
title_fullStr | Virtual Screening of Alkaloid and Terpenoid Inhibitors of SMT Expressed in Naegleria sp. |
title_full_unstemmed | Virtual Screening of Alkaloid and Terpenoid Inhibitors of SMT Expressed in Naegleria sp. |
title_short | Virtual Screening of Alkaloid and Terpenoid Inhibitors of SMT Expressed in Naegleria sp. |
title_sort | virtual screening of alkaloid and terpenoid inhibitors of smt expressed in naegleria sp. |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9457665/ https://www.ncbi.nlm.nih.gov/pubmed/36080504 http://dx.doi.org/10.3390/molecules27175727 |
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