New Potential Antimalarial Agents. Synthesis and Biological Activities of Original Diaza-analogs of Phenanthrene.

Synthesis and Heme Polymerization Inhibitory Activity (HPIA) Assay of Antiplasmodium of (1)-N-(3,4-Dimethoxybenzyl)-1,10-Phenanthrolinium Bromide from Vanillin

“…The organic layer was combined, dried with Na 2 SO 4 anhydrous and evaporated with rotary evaporator to get (4) as yellowish black liquid (85%). This reaction was performed according to the method as previously reported [4]. Compound (4) (1 mmol) and 1,10-phenanthroline monohydrate (1 mmol), and 15 mL acetone were added to a 100 mL three-necked flask.…”

“…According to the previous studies (either experimental and theoretical studies) [2][3][4][5] related with the potential of 1,10-phenanthroline skeleton as the antimalaria, it was predicted that the activity was correlated with the counter anion (I -or Br -), the presence and the charge of benzylic group as well as the nitrogen atom in the phenanthroline. The benzylic group might be introduced via bimolecular substitution reaction between 1,10-phenanthroline and benzyl halide, at which the halide might be varied.…”

“…The group has synthesized and studied the anti plasmodium activity of 1,10-phenanthroline derivatives. Hadanu et al [2], [3] and Yapi et al [4] had synthesized 8 new antiplasmodium of N-alkyl-and Nbenzyl-1,10-phenanthroline and found that N-benzyl-1,10-phenathrolinium iodide displayed very high activity against P. Falciparum strain of FCR3 [5]. The presence of nitrogen atom, softer counter anion and the benzylic group on phenanthroline skeleton was predicted to be responsible to the activity.…”

Antiplasmodial Activity and Acute Toxicity of N-alkyl and N-benzyl-1,10-Phenanthroline Derivatives in Mouse Malaria Model

“…Based on the disadvantages of halofantrine, Yapi et al 4) have synthesized diaza-analogs of phenanthrene by substituting the two nitrogen atoms in the phenanthrene skeleton. In vitro antiplasmodial activity of a series of diaza-analogs of phenanthrene derived from 3-amino, 5-amino, 6-amino, 8-aminoquinoline and 5-aminoisoquinoline showed that among the molecules evaluated the 1,10-phenanthroline skeleton was the most active compound in vitro on both chloroquine-resistant (FcB1) and chloroquine-sensitive (Nigerian) strain with an IC 50 of about 0.13 µM.…”

“…In vitro antiplasmodial activity of a series of diaza-analogs of phenanthrene derived from 3-amino, 5-amino, 6-amino, 8-aminoquinoline and 5-aminoisoquinoline showed that among the molecules evaluated the 1,10-phenanthroline skeleton was the most active compound in vitro on both chloroquine-resistant (FcB1) and chloroquine-sensitive (Nigerian) strain with an IC 50 of about 0.13 µM. Based on the skeleton, Mustofa et al 4) have also synthesized thirteen derivatives of 1,10-phenanthroline and evaluated the in vitro antiplasmodial activity and their structureactivity relationship. Based on the best structureactivity relationship, six new compounds were synthesized: (1)-N-methyl-phenanthrolinium sulfate, (1)-N-ethyl-phenanthrolinium sulfate, (1)-N-benzyl-1,10-phenanthrolinium chloride, (1)-N-benzyl-1,10-phenanthrolinium bromide, (1)-N-benzyl-1,10-phenanthrolinium iodide and (1)-N-(4-metoxy-benzyl)-1,10-phenanthrolinium chloride.…”