Design, synthesis and biological evaluation of fucose-truncated monosaccharide analogues of ipomoeassin F.
Ipomoeassin F is a plant-derived macrocyclic glycolipid with single-digit nanomolar IC50 values against cancer cell growth. In previous structure-activity relationship studies, we have demonstrated that certain modifications around the fucoside moiety did not cause significant cytotoxicity loss. To further elucidate the effect of the fucoside moiety on the biological activity, we describe here the design and synthesis of several fucose-truncated monosaccharide analogues of ipomoeassin F. Subsequent biological evaluation strongly suggests that the 6-membered ring of the fucoside moiety is essential to the overall conformation of the molecule, thereby influencing bioactivity.
['Zong|Guanghui|G|', 'Hirsch|Melissa|M|', 'Mondrik|Collin|C|', 'Hu|Zhijian|Z|', 'Shi|Wei Q|WQ|']
D000972:Antineoplastic Agents, Phytogenic D045744:Cell Line, Tumor D049109:Cell Proliferation D004305:Dose-Response Relationship, Drug D015195:Drug Design D004354:Drug Screening Assays, Antitumor D005643:Fucose D006001:Glycoconjugates D006801:Humans D015394:Molecular Structure D013329:Structure-Activity Relationship
Monosaccharide analogues Ipomoeassin F Cytotoxicity BVBGTMCKLNYQPX-PDDTYTPCSA-N CIWXVLPZBJOWOE-SNVBAGLBSA-N DNGWMNZMRALKSR-IAQQVRHFSA-N GHFRBGNLAWACRU-VJVLEUCCSA-N GSKULKPUBPOPEK-WDYNDCKDSA-N HLKZABNXLHJROG-UHZDTLPASA-N HRNYGVKDTOFUGG-CEGUSXFXSA-N IWTUVIHOHSFHOR-MRFULHKYSA-N KVGYCBMYWWSTJF-ZEBMQPPJSA-N LCSGJDKMNRSKBV-GFCCVEGCSA-N MGRJFGLICMEZQW-UHFFFAOYSA-N MJYFDKSBTYGFMR-NQYVGIDLSA-N MQUBXPPFSCCADG-ZWHJMUPSSA-N Macrolide NDBKVUSDPPZPLV-JJFXFIIRSA-N NDUPBTSXOSZHON-SECBINFHSA-N NNASWLXAHWWJHW-LLVKDONJSA-N ODUVXAVOUUVXHS-OQBDQXSPSA-N ODWBUFIMGGMMCZ-JLKXFGDHSA-N Resin glycosides SUDQQMWMUVLQLI-MHVJIRHVSA-N VSOPGDDGIMCOHZ-IOQCHWBKSA-N WOOTYDFHRXXYOH-WSCIJNKFSA-N ZNKHQZOSZVDWLC-QGLDALQQSA-N