Abstract
The water soluble phosphane complexes [M(L)4]PF6 (M=Cu(I), Ag(I)) and [Au(L)4]Cl (L=thp (tris(hydroxymethyl)phosphane) or PTA (1,3,5-triaza-7-phosphaadamantane)) showed notable in vitro activity against Plasmodium early sporogonic stages, the sexual forms of the malaria parasite that are responsible for infection of the mosquito vector. Effects varied according to both, the type of metal and phosphane ligands. [Ag(thp)4]PF6 was the best performing complex exhibiting a half inhibitory concentration (IC50) value in the low micromolar range (0.3–15.6μM). The silver complex [Ag(thp)4]PF6 was characterized by X-ray crystallography revealing that the structure comprises the cationic complex [Ag(thp)4]+, the PF6− anion, and a water molecule of crystallization. Our results revealed that Cu(I), Ag(I) and Au(I) phosphanes complexes elicited similar activity profiles showing potential for the development of antimalarial, transmission blocking compounds. Molecules targeting the sexual parasite stages in the human and/or mosquito host are urgently needed to complement current artemisinin based treatments and next generation antimalarials in a vision not only to cure the disease but to interrupt its transmission.
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