Syntheses of <span style="font-variant: small-caps">l</span>-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 <span style="font-variant: small-caps;">l</span>-glucosamine-based glycosylated antitumor ether lipi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/3/566 |
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| author | Makanjuola Ogunsina Pranati Samadder Temilolu Idowu Mark Nachtigal Frank Schweizer Gilbert Arthur |
| author_facet | Makanjuola Ogunsina Pranati Samadder Temilolu Idowu Mark Nachtigal Frank Schweizer Gilbert Arthur |
| author_sort | Makanjuola Ogunsina |
| collection | DOAJ |
| 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 <span style="font-variant: small-caps;">l</span>-glucosamine-based glycosylated antitumor ether lipids (GAELs) that were cytotoxic to chemotherapy-resistant cancer cells. In the absence of commercially available <span style="font-variant: small-caps;">l</span>-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 <span style="font-variant: small-caps;">l</span>-sugars including <span style="font-variant: small-caps;">l</span>-rhamnose and <span style="font-variant: small-caps;">l</span>-glucose were developed and the <span style="font-variant: small-caps;">l</span>-GAELs tested for anticancer activity. The most potent analog synthesized, 3-amino-1-<i>O</i>-hexadecyloxy-2R-(<i>O−</i>α-<span style="font-variant: small-caps;">l</span>-rhamnopyranosyl)-<i>sn</i>- glycerol <b>3</b>, 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, <b>3</b> induced cell death by a non-membranolytic caspase-independent pathway. |
| first_indexed | 2024-04-13T04:41:55Z |
| format | Article |
| id | doaj.art-d19affeed2994b37906d0652e9810e13 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T04:41:55Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-d19affeed2994b37906d0652e9810e132022-12-22T03:01:58ZengMDPI AGMolecules1420-30492020-01-0125356610.3390/molecules25030566molecules25030566Syntheses of <span style="font-variant: small-caps">l</span>-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer CellsMakanjuola Ogunsina0Pranati Samadder1Temilolu Idowu2Mark Nachtigal3Frank Schweizer4Gilbert Arthur5Department of Chemistry and Biochemistry, Faculty of Science, University of Manitoba, Winnipeg, MB R3T 2N2, CanadaDepartment of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W9, CanadaDepartment of Chemistry and Biochemistry, Faculty of Science, University of Manitoba, Winnipeg, MB R3T 2N2, CanadaDepartment of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W9, CanadaDepartment of Chemistry and Biochemistry, Faculty of Science, University of Manitoba, Winnipeg, MB R3T 2N2, CanadaDepartment of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W9, CanadaA major impediment to successful cancer treatment is the inability of clinically available drugs to kill drug-resistant cancer cells. We recently identified metabolically stable <span style="font-variant: small-caps;">l</span>-glucosamine-based glycosylated antitumor ether lipids (GAELs) that were cytotoxic to chemotherapy-resistant cancer cells. In the absence of commercially available <span style="font-variant: small-caps;">l</span>-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 <span style="font-variant: small-caps;">l</span>-sugars including <span style="font-variant: small-caps;">l</span>-rhamnose and <span style="font-variant: small-caps;">l</span>-glucose were developed and the <span style="font-variant: small-caps;">l</span>-GAELs tested for anticancer activity. The most potent analog synthesized, 3-amino-1-<i>O</i>-hexadecyloxy-2R-(<i>O−</i>α-<span style="font-variant: small-caps;">l</span>-rhamnopyranosyl)-<i>sn</i>- glycerol <b>3</b>, 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, <b>3</b> induced cell death by a non-membranolytic caspase-independent pathway.https://www.mdpi.com/1420-3049/25/3/566glycosylated antitumor ether lipids<span style="font-variant: small-caps">l</span>-rhamnose-based glycolipidschemotherapy resistantcaspase independent |
| spellingShingle | Makanjuola Ogunsina Pranati Samadder Temilolu Idowu Mark Nachtigal Frank Schweizer Gilbert Arthur Syntheses of <span style="font-variant: small-caps">l</span>-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer Cells Molecules glycosylated antitumor ether lipids <span style="font-variant: small-caps">l</span>-rhamnose-based glycolipids chemotherapy resistant caspase independent |
| title | Syntheses of <span style="font-variant: small-caps">l</span>-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer Cells |
| title_full | Syntheses of <span style="font-variant: small-caps">l</span>-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer Cells |
| title_fullStr | Syntheses of <span style="font-variant: small-caps">l</span>-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer Cells |
| title_full_unstemmed | Syntheses of <span style="font-variant: small-caps">l</span>-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer Cells |
| title_short | Syntheses of <span style="font-variant: small-caps">l</span>-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer Cells |
| title_sort | syntheses of span style font variant small caps l span rhamnose linked amino glycerolipids and their cytotoxic activities against human cancer cells |
| topic | glycosylated antitumor ether lipids <span style="font-variant: small-caps">l</span>-rhamnose-based glycolipids chemotherapy resistant caspase independent |
| url | https://www.mdpi.com/1420-3049/25/3/566 |
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