Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; Department of Medicine, University of Cape Town, K45, OMB, Groote Schuur Hospital, Observatory 7925, South Africa; Division of Medical Biochemistry, Department of Clinical and Laboratory Sciences, University of Cape Town, Rondebosch 7701, South Africa; MRC/NHLS/UCT Molecular Mycobacteriology Research Unit, DST/NRF Centre of Excellence for Biomedical TB Research, University of Cape Town, Rondebosch 7701, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa
Li, Y., Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; De Kock, C., Department of Medicine, University of Cape Town, K45, OMB, Groote Schuur Hospital, Observatory 7925, South Africa; Smith, P.J., Department of Medicine, University of Cape Town, K45, OMB, Groote Schuur Hospital, Observatory 7925, South Africa; Guzgay, H., Division of Medical Biochemistry, Department of Clinical and Laboratory Sciences, University of Cape Town, Rondebosch 7701, South Africa; Hendricks, D.T., Division of Medical Biochemistry, Department of Clinical and Laboratory Sciences, University of Cape Town, Rondebosch 7701, South Africa; Naran, K., MRC/NHLS/UCT Molecular Mycobacteriology Research Unit, DST/NRF Centre of Excellence for Biomedical TB Research, University of Cape Town, Rondebosch 7701, South Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa; Mizrahi, V., MRC/NHLS/UCT Molecular Mycobacteriology Research Unit, DST/NRF Centre of Excellence for Biomedical TB Research, University of Cape Town, Rondebosch 7701, South Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa; Warner, D.F., MRC/NHLS/UCT Molecular Mycobacteriology Research Unit, DST/NRF Centre of Excellence for Biomedical TB Research, University of Cape Town, Rondebosch 7701, South Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa; Chibale, K., Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa; Smith, G.S., Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
Two silicon-containing analogues (1, 2) of chloroquine, modified in the lateral side chain with organosilicon moieties, were synthesized. Compounds 1 and 2 were further reacted with dinuclear half-sandwich transition metal precursors [Ru(Ar)(μ-Cl)Cl]2 (Ar = η6-p- iPrC6H4Me; η6-C 6H6; η6-C6H5OCH 2CH2OH), [Rh(COD)(μ-Cl)]2, and [RhCp*(μ-Cl)Cl]2, to yield a series of neutral mononuclear Ru(II), Rh(I), and Rh(III) silicon-aminoquinoline complexes (3-12). Compounds 1 and 2 act as monodentate donors that coordinate to the transition metals via the quinoline nitrogen of the aminoquinoline scaffold. All the compounds were characterized using various analytical and spectroscopic techniques, and the molecular structures of compounds 2 and 11 were elucidated by single-crystal X-ray diffraction analysis. Furthermore, the in vitro pharmacological activities of compounds 1-12 were established against chloroquine-sensitive (NF54) and chloroquine-resistant (Dd2) strains of the malarial parasite Plasmodium falciparum and against the pathogenic bacterium Mycobacterium tuberculosis H37Rv, as well as an esophageal (WHCO1) cancer cell line. © 2012 American Chemical Society.