In vitro antiplasmodial activity and cytotoxicity of newly synthesized N-alkyl and N-benzyl-1,10-phenanthroline derivatives.
A previous study showed that the 1,10-phenanthroline skeleton was active in vitro against chloroquine-resistant and sensitive strains of Plasmodium falciparum. Based on this skeleton, 8 derivatives of N-alkyl and N-benzyl-1,10-phenanthrolines have been synthesized. This study was conducted to evaluate the in vitro antiplasmodial activity and cytotoxicity of these compounds. The in vitro antiplasmodial activity was tested on two strains of P. falciparum, FCR-3 chloroquine-resistant and D10 chloroquine-sensitive strains, while their cytotoxicity was tested on the Vero cell line. The parasite and cell growth were estimated by hypoxantine-[2,8-3H] uptake after 24- and 72-hour incubation with each compound tested. The control parasite or cell free from any compounds was referred to as having 100% growth. For this radioactive method, the IC50 value showing concentration inhibiting 50% of the parasite growth was determined by probit analysis. The results showed that the highest antiplasmodial activity was observed with (1)-N-benzyl-1,10-phenanthrolinium iodide with the IC50 0.18-0.45 microM, and the IC50 of the compound on Vero cells ranged from 2,582.30 to 7,057.71 microM. The cytotoxic/ antiplasmodial ratio indicates that this compound has high selectivity (10,993 +/- 330.79-38,965 +/- 6,888.27).
Sholikhah
Eti Nurwening
EN
Department of Pharmacology and Toxicology, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia. etiwening@yahoo.com
Supargiyono
Jumina
Wijayanti
Mahardika Agus
MA
Tahir
Iqmal
I
Hadanu
Ruslin
R
Mustofa
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D002738:Chloroquine / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004351:Drug Resistance; D066298:In Vitro Techniques; D007214:Indonesia; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D026901:Membrane Transport Proteins / Q000187:drug effects*; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D015800:Protozoan Proteins / Q000187:drug effects*; D014709:Vero Cells / Q000187:drug effects
D002614:Chelating Agents; D002800:Cholinesterase Inhibitors; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D010618:Phenanthrolines; D015800:Protozoan Proteins; D002738:Chloroquine; C025205:1,10-phenanthroline