Synthesis and Antimalarial Activity of 2-Phenyl-1,10-Phenanthroline Derivative Compounds

Abstract

To develop new potential antimalarial drugs of 2-phenyl-1,10-phenanthroline 5 derivatives from 8-aminoquinoline as starting material were synthesized in good yields. The synthesis of 2-phenyl-1,10-phenanthroline 5 derivatives compounds with 8-aminoquinoline 4 as starting material through three steps has been carried out. The first step of reactions is aldol condensation of benzaldehyde 1 with acetaldehyde 2. The result of reactions is cinnamaldehyde 3 (92.14%) in the form of yellow solid. The second step of reactions was synthesized of 2-phenyl-1,10-phenanthroline 5 (brown solid, 54.63%) through cyclization of 8-aminoquinoline 4 with cinnamaldehyde 3 compound. The third step of reactions is methylation and ethylation of 2-phenyl-1,10-phenanthroline using dimethyl sulphate (DMS) and diethyl sulphate (DES) reagents that it was refluxed for 17 and 19 h, respectively. The results of reactions are (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate 6 and (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate 7 in yield from 90.62% and 89.70%, respectively. The results of testing in vitro antiplasmodial activity at chloroquine-resistant Plasmodium falciparum FCR3 strain to 2-phenyl-1,10phenanthroline 5 derivatives obtained that (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate 7 compound has higher antimalarial activity (IC 50 :0.13 ± 0.02 µM) than antimalarial activity of (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate 6 compound (IC 50 :0.25 ± 0.01 µM) and 2-phenyl-1,10-phenanthroline 5 compound (IC 50 :2.45 ± 0.09 µM). While, the results of testing in vitro antiplasmodial activity at chloroquine-resistant Plasmodium falciparum D10 strain to 2-phenyl-1,10phenanthroline 5 derivatives obtained that (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate 6 compound has higher antimalarial activity (IC 50 :0.10± 0.04 µM) than antimalarial activity of (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate 7 (IC 50 :0.18 ± 0.01 µM) and 2-phenyl-1,10-phenanthroline 5 compound (IC 50 :0.55 ± 0.07 µM).

Synthesis of 1-(2-Methoxybenzyl)-1,10-phenanthrolin-1-ium Bromide from Gandapura Oil

“…In this report, we have prepared 1-(2-methoxybenzyl)-1,10-phenanthrolin-1-ium bromide from readily available starting materials via simple synthetic methods. The new compound may contribute to the construction of our small library of 1-(N)-substituted-1,10phenanthrolinium salts [7][8][9][10][11][12] and were expected to have biological activities. From a synthetic point of view, 1-(2-methoxybenzyl)-1,10-phenanthrolin-1-ium bromide can be simply disconnected to give benzyl halides and 1,10-phenanthroline via bimolecular nucleophilic substitution.…”

“…In the connection to the pharmaceutical applications, our group have prepared a small library of 1-(N)-substituted-1,10-phenanthrolinium salts [7][8][9][10][11][12]. These compounds were then subjected to in vitro and in vivo anti plasmodium assay against two strains of Plasmodium falciparum of FCR3 (resistance to chloroquine) and D10 (sensitive to chloroquine) [12][13][14][15]. We found that 1-(N)-benzylated-1,10-phenanthrolinium salts exhibited good activity against the parasite and have high potentials to be further developed.…”