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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).