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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...

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Detalles Bibliográficos
Autores principales: Ogunsina, Makanjuola, Samadder, Pranati, Idowu, Temilolu, Nachtigal, Mark, Schweizer, Frank, Arthur, Gilbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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
Descripción
Sumario: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.