Syntheses of <span style="font-variant: small-caps">l</span>-Rhamnose-Linked Amino Glycerolipids and Their Cytotoxic Activities against Human Cancer Cells
oleh: Makanjuola Ogunsina, Pranati Samadder, Temilolu Idowu, Mark Nachtigal, Frank Schweizer, Gilbert Arthur
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2020-01-01 |
Deskripsi
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.