Synthesis, Characterization, and Pharmacological Evaluation of Silicon-Containing Aminoquinoline Organometallic Complexes As Antiplasmodial, Antitumor, and Antimycobacterial Agents

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)(mu-Cl)Cl](2) (Ar = eta(6)-p-(PrC6H4Me)-Pr-i; eta(6)-C6H6; eta(6)-C6H5OCH2CH2OH), [Rh(COD)(mu-Cl)](2), and [RhCp*(mu-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.