title: Synthesis, antimalarial evaluation and molecular modeling studies of hydroxyethylpiperazines, potential aspartyl protease inhibitors, part 2.
abstract: 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.
authors.affiliation: Departamento de Síntese, Farmanguinhos-Fiocruz, R. Sizenando Nabuco 100, 21041-250 Rio de Janeiro, RJ, Brazil. wjcunico@yahoo.com.br
authors.forename: Wilson
authors.initials: W
authors.lastname: Cunico
authors.forename: Claudia R B
authors.initials: CR
authors.lastname: Gomes
authors.forename: Victor
authors.initials: V
authors.lastname: Facchinetti
authors.forename: Marcele
authors.initials: M
authors.lastname: Moreth
authors.forename: Carmen
authors.initials: C
authors.lastname: Penido
authors.forename: Maria G M O
authors.initials: MG
authors.lastname: Henriques
authors.forename: Fernando P
authors.initials: FP
authors.lastname: Varotti
authors.forename: Luisa G
authors.initials: LG
authors.lastname: Krettli
authors.forename: Antoniana U
authors.initials: AU
authors.lastname: Krettli
authors.forename: Franklin S
authors.initials: FS
authors.lastname: da Silva
authors.forename: Ernesto R
authors.initials: ER
authors.lastname: Caffarena
authors.forename: Camila S
authors.initials: CS
authors.lastname: de Magalhães
mesh_terms: 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
chemical_list: D000962:Antimalarials; D004983:Ethanolamines; D015800:Protozoan Proteins; D016282:Aspartic Acid Endopeptidases; C100637:plasmepsin II