Synthesis, antimalarial evaluation and molecular modeling studies of hydroxyethylpiperazines, potential aspartyl protease inhibitors, part 2.
The antimalarial acitivity of hydroxyethylamines, synthesized from the reaction of intermediated hydroxyethypiperazines with benzenesulfonyl chlorides or benzoyl chlorides, has been evaluated in vitro against a W2 Plasmodium falciparum clone. Some of the nineteen tested derivatives showed a significant activity in vitro, thus turning into a promising new class of antimalarials. In addition, a molecular modeling study of the most active derivative (5l) was performed and its most probable binding modes within plasmepsin II enzyme were identified.
Cunico
Wilson
W
Departamento de Síntese, Farmanguinhos-Fiocruz, R. Sizenando Nabuco 100, 21041-250 Rio de Janeiro, RJ, Brazil. wjcunico@yahoo.com.br
Gomes
Claudia R B
CR
Facchinetti
Victor
V
Moreth
Marcele
M
Penido
Carmen
C
Henriques
Maria G M O
MG
Varotti
Fernando P
FP
Krettli
Luisa G
LG
Krettli
Antoniana U
AU
da Silva
Franklin S
FS
Caffarena
Ernesto R
ER
de Magalhães
Camila S
CS
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D002460:Cell Line; D004912:Erythrocytes / Q000469:parasitology; D004983:Ethanolamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008958:Models, Molecular; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D051189:Murinae; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism
D000962:Antimalarials; D004983:Ethanolamines; D015800:Protozoan Proteins; D016282:Aspartic Acid Endopeptidases; C100637:plasmepsin II