Synthesis, cytotoxicity and antimalarial activity of ferrocenyl amides of 4-aminoquinolines.
Series of 4-aminoquinolines bearing an amino side chain linked to the ferrocene moiety through an amide bond were synthesized and evaluated for their antimalarial activity against both chloroquine-sensitive (D10, CQ-S) and chloroquine-resistant (Dd2, CQ-R) strains of Plasmodium falciparum. They were also tested for cytotoxicity against Chinese Hamster Ovarian (CHO) cells. Amide 12 featuring propyl side chain linked to the ferrocene ring was the most active of all tested compounds. With an IC50 value of 0.08 microg/mL, this amide showed 1.5-fold higher activity than chloroquine diphosphate (IC50 = 0.12 microg/mL) against the resistant strain, with a selectivity index of 550 indicating its high selectivity towards the parasite. Derivatives which were equipotent against both strains also showed up to ten-fold increase in activity compared to primaquine.
Department of Pharmaceutical Chemistry, School Pharmacy, North-West University, Potchefstroom, South Africa. david.nda@nwu.ac.za
David D
DD
N'Da
Jaco C
JC
Breytenbach
Peter J
PJ
Smith
Carmen
C
Lategan
D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology*; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D005296:Ferrous Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D000075163:Metallocenes; D010963:Plasmodium falciparum / Q000187:drug effects
D000634:Aminoquinolines; D000962:Antimalarials; D000972:Antineoplastic Agents, Phytogenic; D005296:Ferrous Compounds; D007202:Indicators and Reagents; D000075163:Metallocenes; D002738:Chloroquine; C004998:ferrocene