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Syntheses of l-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer Cells
A major impediment to successful cancer treatment is the inability of clinically available drugs to kill drug-resistant cancer cells. We recently identified metabolically stable l-glucosamine-based glycosylated antitumor ether lipids (GAELs) that were cytotoxic to chemotherapy-resistant cancer cells...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037447/ https://www.ncbi.nlm.nih.gov/pubmed/32012953 http://dx.doi.org/10.3390/molecules25030566 |
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author | Ogunsina, Makanjuola Samadder, Pranati Idowu, Temilolu Nachtigal, Mark Schweizer, Frank Arthur, Gilbert |
author_facet | Ogunsina, Makanjuola Samadder, Pranati Idowu, Temilolu Nachtigal, Mark Schweizer, Frank Arthur, Gilbert |
author_sort | Ogunsina, Makanjuola |
collection | PubMed |
description | A major impediment to successful cancer treatment is the inability of clinically available drugs to kill drug-resistant cancer cells. We recently identified metabolically stable l-glucosamine-based glycosylated antitumor ether lipids (GAELs) that were cytotoxic to chemotherapy-resistant cancer cells. In the absence of commercially available l-glucosamine, many steps were needed to synthesize the compound and the overall yield was poor. To overcome this limitation, a facile synthetic procedure using commercially available l-sugars including l-rhamnose and l-glucose were developed and the l-GAELs tested for anticancer activity. The most potent analog synthesized, 3-amino-1-O-hexadecyloxy-2R-(O–α-l-rhamnopyranosyl)-sn- glycerol 3, demonstrated a potent antitumor effect against human cancer cell lines derived from breast, prostate, and pancreas. The activity observed was superior to that observed with clinical anticancer agents including cisplatin and chlorambucil. Moreover, like other GAELs, 3 induced cell death by a non-membranolytic caspase-independent pathway. |
format | Online Article Text |
id | pubmed-7037447 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70374472020-03-11 Syntheses of l-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer Cells Ogunsina, Makanjuola Samadder, Pranati Idowu, Temilolu Nachtigal, Mark Schweizer, Frank Arthur, Gilbert Molecules Article A major impediment to successful cancer treatment is the inability of clinically available drugs to kill drug-resistant cancer cells. We recently identified metabolically stable l-glucosamine-based glycosylated antitumor ether lipids (GAELs) that were cytotoxic to chemotherapy-resistant cancer cells. In the absence of commercially available l-glucosamine, many steps were needed to synthesize the compound and the overall yield was poor. To overcome this limitation, a facile synthetic procedure using commercially available l-sugars including l-rhamnose and l-glucose were developed and the l-GAELs tested for anticancer activity. The most potent analog synthesized, 3-amino-1-O-hexadecyloxy-2R-(O–α-l-rhamnopyranosyl)-sn- glycerol 3, demonstrated a potent antitumor effect against human cancer cell lines derived from breast, prostate, and pancreas. The activity observed was superior to that observed with clinical anticancer agents including cisplatin and chlorambucil. Moreover, like other GAELs, 3 induced cell death by a non-membranolytic caspase-independent pathway. MDPI 2020-01-28 /pmc/articles/PMC7037447/ /pubmed/32012953 http://dx.doi.org/10.3390/molecules25030566 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ogunsina, Makanjuola Samadder, Pranati Idowu, Temilolu Nachtigal, Mark Schweizer, Frank Arthur, Gilbert Syntheses of l-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer Cells |
title | Syntheses of l-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer Cells |
title_full | Syntheses of l-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer Cells |
title_fullStr | Syntheses of l-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer Cells |
title_full_unstemmed | Syntheses of l-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer Cells |
title_short | Syntheses of l-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer Cells |
title_sort | syntheses of l-rhamnose-linked amino glycerolipids and their cytotoxic activities against human cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037447/ https://www.ncbi.nlm.nih.gov/pubmed/32012953 http://dx.doi.org/10.3390/molecules25030566 |
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