The bisnaphthalimides as new active lead compounds against Plasmodium falciparum.
The bisquaternary bisnaphthalimides are a versatile class of compounds being active against the malaria parasite Plasmodium falciparum in the lower nanomolar range of concentration combined with no cytotoxicity. The series of compounds is designed as choline analogues and interfering agents of the phosphatidylcholine biosynthesis. The qualitative analysis of the structure-activity relationships (SAR) revealed the importance of a long methylene middle chain of at least 8 methylene groups between the two bisquaternary naphthalimides or a monoquaternary naphthalimide consisting of a long alkyl chain attached to the positively charged nitrogen atom. Since the SARs are different from reported biscationic antimalarial drugs the mode of action remains to be elucidated.
Tischer
Maximilian
M
Institute of Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, Germany.
Sologub
Ludmilla
L
Pradel
Gabriele
G
Holzgrabe
Ulrike
U
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002460:Cell Line; D008264:Macrophages / Q000648:ultrastructure; D015394:Molecular Structure; D053644:Naphthalimides / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000648:ultrastructure; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000962:Antimalarials; D053644:Naphthalimides; D000644:Quaternary Ammonium Compounds