title: New pentasubstituted pyrrole hybrid atorvastatin-quinoline derivatives with antiplasmodial activity.
abstract: Cerebral malaria is caused by Plasmodium falciparum. Atorvastatin (AVA) is a pentasubstituted pyrrole, which has been tested as an adjuvant in the treatment of cerebral malaria. Herein, a new class of hybrids of AVA and aminoquinolines (primaquine and chloroquine derivatives) has been synthesized. The quinolinic moiety was connected to the pentasubstituted pyrrole from AVA by a linker group (CH2)n=2-4 units. The activity of the compounds increased with the size of the carbons chain. Compound with n=4 and 7-chloroquinolinyl has displayed better activity (IC50=0.40 μM) than chloroquine. The primaquine derivative showed IC50=1.41 μM, being less toxic and more active than primaquine.
authors.affiliation: Departamento de Síntese de Fármacos, Instituto de Tecnologia em Fármacos, Farmanguinhos-FIOCRUZ, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro, RJ 21041-250, Brazil; Programa de Pós Graduação em Química, PGQu Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Rita C C
authors.initials: RC
authors.lastname: Carvalho
authors.affiliation: Departamento de Síntese de Fármacos, Instituto de Tecnologia em Fármacos, Farmanguinhos-FIOCRUZ, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro, RJ 21041-250, Brazil.
authors.forename: Wagner A
authors.initials: WA
authors.lastname: Martins
authors.affiliation: Laboratório de Malária, Centro de Pesquisas René Rachou, CPqRR-FIOCRUZ, Belo Horizonte, MG 30190-002, Brazil.
authors.forename: Tayara P
authors.initials: TP
authors.lastname: Silva
authors.affiliation: Programa de Pós Graduação em Química, PGQu Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Kaiser
authors.affiliation: Departamento de Síntese de Fármacos, Instituto de Tecnologia em Fármacos, Farmanguinhos-FIOCRUZ, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro, RJ 21041-250, Brazil.
authors.forename: Mônica M
authors.initials: MM
authors.lastname: Bastos
authors.affiliation: Departamento de Síntese de Fármacos, Instituto de Tecnologia em Fármacos, Farmanguinhos-FIOCRUZ, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro, RJ 21041-250, Brazil.
authors.forename: Luiz C S
authors.initials: LC
authors.lastname: Pinheiro
authors.affiliation: Laboratório de Malária, Centro de Pesquisas René Rachou, CPqRR-FIOCRUZ, Belo Horizonte, MG 30190-002, Brazil.
authors.forename: Antoniana U
authors.initials: AU
authors.lastname: Krettli
authors.affiliation: Departamento de Síntese de Fármacos, Instituto de Tecnologia em Fármacos, Farmanguinhos-FIOCRUZ, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro, RJ 21041-250, Brazil. Electronic address: boechat@far.fiocruz.br.
authors.forename: Núbia
authors.initials: N
authors.lastname: Boechat
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000069059:Atorvastatin / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D011758:Pyrroles; D011804:Quinolines; D000069059:Atorvastatin; C037219:quinoline
keywords: Atorvastatin; Chloroquine; Malaria; Pentasubstituted pyrrole; Primaquine