title: In vitro antiplasmodial activity and cytotoxicity of newly synthesized N-alkyl and N-benzyl-1,10-phenanthroline derivatives.
abstract: 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).
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia. etiwening@yahoo.com
authors.forename: Eti Nurwening
authors.initials: EN
authors.lastname: Sholikhah
authors.lastname: Supargiyono
authors.lastname: Jumina
authors.forename: Mahardika Agus
authors.initials: MA
authors.lastname: Wijayanti
authors.forename: Iqmal
authors.initials: I
authors.lastname: Tahir
authors.forename: Ruslin
authors.initials: R
authors.lastname: Hadanu
authors.lastname: Mustofa
mesh_terms: 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
chemical_list: 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