title: Synthesis and antimalarial activity of new heterocyclic hybrids based on chloroquine and thiazolidinone scaffolds.
abstract: A series of new 21 chloroquine heterocyclic hybrids containing either benzylamino fragment or N-(aminoalkyl)thiazolidin-4-one moiety were synthesized and screened for their antimalarial activity against chloroquine (CQ)-sensitive 3D7 and multidrug-resistance Dd2 strains of Plasmodium falciparum. Although no compounds more active than CQ against 3D7 was found; against Dd2 strain, six compounds, four of them with benzylamino fragment, showed an excellent activity, up to 3-fold more active than CQ. Non specific cytotoxicity on J774 macrophages was observed in some compounds whereas only two of them showed liver toxicity on HepG2 cells. In addition, all active compounds inhibited the ferriprotoporphyrin IX biocrystalization process in concentrations around to CQ. In vivo preliminary results have shown that at least two compounds are as active as CQ against Plasmodium berghei ANKA.
authors: Laboratorio de Química Orgánica y Biomolecular, Escuela de Química, Universidad Industrial de Santander, A. A. 678, Bucaramanga, Colombia.
authors: Fernando A
authors: FA
authors: Rojas Ruiz
authors: Rory N
authors: RN
authors: García-Sánchez
authors: Santiago Villabona
authors: SV
authors: Estupiñan
authors: Alicia
authors: A
authors: Gómez-Barrio
authors: Diego F
authors: DF
authors: Torres Amado
authors: Berta Martín
authors: BM
authors: Pérez-Solórzano
authors: Juan J
authors: JJ
authors: Nogal-Ruiz
authors: Antonio R
authors: AR
authors: Martínez-Fernández
authors: Vladimir V
authors: VV
authors: Kouznetsov
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D056945:Hep G2 Cells; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects*; D053778:Thiazolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D053778:Thiazolidines; D002738:Chloroquine