Design, synthesis and antimalarial/anticancer evaluation of spermidine linked artemisinin conjugates designed to exploit polyamine transporters in Plasmodium falciparum and HL-60 cancer cell lines.
A series of artemisinin-spermidine conjugates designed to utilise the upregulated polyamine transporter found in cancer cells have been prepared. These conjugates were evaluated against human promyelocytic leukaemia HL-60 cells and chloroquine-sensitive 3D7 Plasmodium falciparum and several show promising anticancer and antimalarial activity. Although some limitations in this vector-based approach are apparent, a number of high potency Boc-protected analogues were identified with activity against malaria parasites as low as 0.21nM.
Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK.
James
J
Chadwick
Michael
M
Jones
Amy E
AE
Mercer
Paul A
PA
Stocks
Stephen A
SA
Ward
B Kevin
BK
Park
Paul M
PM
O'Neill
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology*; D037621:Artemisinins / Q000138:chemical synthesis* / Q000494:pharmacology*; D015317:Biogenic Polyamines / Q000378:metabolism*; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism*; D004396:Coloring Agents; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism*; D013095:Spermidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles
D000962:Antimalarials; D000972:Antineoplastic Agents, Phytogenic; D037621:Artemisinins; D015317:Biogenic Polyamines; D002352:Carrier Proteins; D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; C031327:artemisinin; C022616:thiazolyl blue; D013095:Spermidine