Jacobs L., De Kock C., De Villiers K.A., Smith P.J., Smith V.J., Van Otterlo W.A.L., Blackie M.A.L.
Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland, South Africa; Department of Pharmacology, University of Cape Town, Private Bag X2 Rondebosch, Cape Town, South Africa
Jacobs, L., Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland, South Africa; De Kock, C., Department of Pharmacology, University of Cape Town, Private Bag X2 Rondebosch, Cape Town, South Africa; De Villiers, K.A., Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland, South Africa; Smith, P.J., Department of Pharmacology, University of Cape Town, Private Bag X2 Rondebosch, Cape Town, South Africa; Smith, V.J., Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland, South Africa; Van Otterlo, W.A.L., Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland, South Africa; Blackie, M.A.L., Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland, South Africa
7-Chloroquinoline-based antimalarial drugs are effective in the inhibition of hemozoin formation in the food vacuole of the Plasmodium parasite, the causative agent of malaria. We synthesized five series of ferroquine (FQ) and phenylequine (PQ) derivatives, which display good in vitro efficacy toward both the chloroquine-sensitive (CQS) NF54 (IC50: 4.2 nm) and chloroquine-resistant (CQR) Dd2 (IC50: 33.7 nm) strains of P. falciparum. Several compounds were found to have good inhibitory activity against β-hematin formation in an NP-40 detergent assay, with IC50 values ranging between 10.4 and 19.2 μm. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
antimalarial agent; aromatic amine; artesunate; beta hematin; chloroquine; ethyl 2 [[2 (7 chloroquinolin 4 ylamino)ethyl] [2 [(dimethylamino)methyl]benzyl]amino] 2 oxoacetate; ethyl 2 [[3 (7 chloroquinolin 4 ylamino)propyl] [2 [(dimethylamino)methyl]benzyl]amino] 2 oxoacetate; ferroquine; hematin; n 1 (7 chloroquinolin 4 yl) n 2 [2 [(dimethylamino)methyl]benzyl]butan 1,4 diamine; n 1 (7 chloroquinolin 4 yl) n 2 [2 [(dimethylamino)methyl]benzyl]hexan 1,6 diamine; n 1 (7 chloroquinolin 4 yl) n 2 [2 [(dimethylamino)methyl]ferrocenylmethyl]ethan 1,2 diamine; n 1 (7 chloroquinolin 4 yl) n 3 [2 [(dimethylamino)methyl]ferrocenylmethyl]propan 1,3 diamine; n 1 (7 chloroquinolin 4 yl) n 4 [2 [(dimethylamino)methyl]ferrocenylmethyl]butan 1,4 diamine; n 1 (7 chloroquinolin 4 yl) n 5 [2 [(dimethylamino)methyl]benzyl]pentan 1,5 diamine; n 1 (7 chloroquinolin 4 yl) n 5 [2 [(dimethylamino)methyl]ferrocenylmethyl]penta 1,5 diamine; n 1 (7 chloroquinolin 4 yl) n 6 [2 [(dimethylamino)methyl]benzyl]hexan 1,6 diamine; n 1 (7 chloroquinolin 4 yl) n 6 [2 [(dimethylamino)methyl]ferrocenylmethyl]hexane 1,6 diamine; n 1 [2 (7 chloroquinolin 4 ylamino)ethyl] n 2 [2 [(dimethylamino)methyl]benzyl]oxalamide; n 1 [2 (7 chloroquinolin 4 ylamino)ethyl] n 2 [2 [(dimethylamino)methyl]ferrocenylmethyl]oxalamide; n 1 [2 (7 chloroquinolin 4 ylamino)ethyl] n 4 [2 [(dimethylamino)methyl]ferrocenylmethyl]oxalamide; n 1 [3 (7 chloroquinolin 4 ylamino)ethyl] n 3 [2 [(dimethylamino)methyl]benzyl]oxalamide; n 1 [3 (7 chloroquinolin 4 ylamino)ethyl] n 3 [2 [(dimethylamino)methyl]ferrocenylmethyl]oxalamide; n 1 [4 (7 chloroquinolin 4 ylamino)ethyl] n 4 [2 [(dimethylamino)methyl]benzyl]oxalamide; n 1 [4 (7 chloroquinolin 4 ylamino)ethyl] n 4 [2 [(dimethylamino)methyl]ferrocenylmethyl]oxalamide; n 1 [5 (7 chloroquinolin 4 ylamino)ethyl] n 5 [2 [(dimethylamino)methyl]ferrocenylmethyl]oxalamide; n 1 [6 (7 chloroquinolin 4 ylamino)ethyl] n 6 [2 [(dimethylamino)methyl]benzyl]oxalamide; n 1 [6 (7 chloroquinolin 4 ylamino)ethyl] n 6 [2 [(dimethylamino)methyl]ferrocenylmethyl]oxalamide; phenylequine derivative; unclassified drug; unindexed drug; antimalarial activity; antimalarial drug resistance; Article; carbon nuclear magnetic resonance; cross resistance; drug design; drug efficacy; drug screening; drug synthesis; follow up; hydrogen bond; IC50; in vitro study; infrared spectroscopy; nonhuman; Plasmodium falciparum; priority journal; proton nuclear magnetic resonance; X ray diffraction