Annonaceous acetogenin mimics bearing a terminal lactam and their cytotoxicity against cancer cells.
Annonaceous acetogenins are a large class of naturally occurring polyketides exhibiting potent anticancer activities. Based on our previous discovery of AA005, a multi-ether mimic of natural acetogenins having potent antitumor activities and significant selectivity between normal cells and cancer cells, a new series of mimics containing a terminal lactam were designed, synthesized and evaluated. Bioactivity study against cancer cells shows that the N-methylated lactam-containing compounds 3, 4, and 5 exhibit comparable potencies to that of AA005, as well as the similar selectivity to cancer cells. Hydrocarbon-length effects of N-alkyl were further explored through synthesizing derivatives 24-26, and application of this derivation protocol to the fluorescent labeling was also investigated.
Liu
Hai-Xia
HX
State Key Laboratory of Bioorganic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China.
Huang
Guo-Rui
GR
Zhang
Huan-Ming
HM
Wu
Jia-Rui
JR
Yao
Zhu-Jun
ZJ
D054378:Acetogenins; D000473:Alkanes / Q000737:chemistry; D029061:Annonaceae / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D007769:Lactams / Q000138:chemical synthesis / Q000494:pharmacology*; D007783:Lactones / Q000737:chemistry*; D008956:Models, Chemical; D018716:Molecular Mimicry; D014407:Tumor Cells, Cultured / Q000187:drug effects
C483824:AA005; D054378:Acetogenins; D000473:Alkanes; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D005233:Fatty Alcohols; D005456:Fluorescent Dyes; D007769:Lactams; D007783:Lactones