Outstanding plasmodicidal properties within a small panel of metallic compounds: Hints for the development of new metal-based antimalarials.
A variegate group of metallodrugs was evaluated in vitro for antimalarial activity through the pLDH test. The panel comprised one mononuclear gold(III) complex, (Aubipy), three dinuclear gold(III) compounds (Auoxo4, Auoxo5 and Auoxo6), three ruthenium(III) complexes (NAMI A, PMRU20, PMRU27), one ruthenium(II) complex (PMRU52), one bismuth(III) compound (Bismuth citrate), antimony trichloride (SbCl(3)) and arsenic trioxide (As(2)O(3)). This panel, although relatively small, was built up in such a way to include a variety of metal centers, structural motifs and metal coordination environments. In general, the tested compounds turned out to contrast effectively Plasmodium falciparum growth in vitro. In two cases, i.e. NAMI A and antimony trichloride, IC(50) values in the high nanomolar range were measured. Notably, the antiplasmodial effects appear not to be correlated to in vitro anticancer properties. The mechanistic and pharmacological implications of the obtained results are discussed.
Gabbiani
Chiara
C
Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy.
Messori
Luigi
L
Cinellu
Maria A
MA
Casini
Angela
A
Mura
Pasquale
P
Sannella
Anna R
AR
Severini
Carlo
C
Majori
Giancarlo
G
Bilia
Anna R
AR
Vincieri
Franco F
FF
D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007770:L-Lactate Dehydrogenase / Q000187:drug effects*; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology
D000962:Antimalarials; D009942:Organometallic Compounds; D007770:L-Lactate Dehydrogenase