Novel metalloantimalarials: Transmission blocking effects of water soluble Cu(I), Ag(I) and Au(I) phosphane complexes on the murine malaria parasite Plasmodium berghei.
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]PF6was 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]PF6was 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.
School of Pharmacy, University of Camerino, Piazza dei Costanti, Camerino, MC, Italy.
Sofia
S
Tapanelli
School of Pharmacy, University of Camerino, Piazza dei Costanti, Camerino, MC, Italy. Electronic address: annette.habluetzel@unicam.it.
Annette
A
Habluetzel
School of Science and Technology - Chemistry Division, University of Camerino, via S. Agostino 1, Camerino, MC, Italy. Electronic address: maura.pellei@unicam.it.
Maura
M
Pellei
Department of Chemistry, University of Parma, Parco Area delle Scienze 17A, Parma, Italy.
Luciano
L
Marchiò
School of Science and Technology - Chemistry Division, University of Camerino, via S. Agostino 1, Camerino, MC, Italy.
Alessia
A
Tombesi
School of Science and Technology - Chemistry Division, University of Camerino, via S. Agostino 1, Camerino, MC, Italy.
Ambra
A
Capparè
School of Science and Technology - Chemistry Division, University of Camerino, via S. Agostino 1, Camerino, MC, Italy.
Carlo
C
Santini
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003300:Copper / Q000737:chemistry / Q000494:pharmacology; D006046:Gold / Q000737:chemistry / Q000494:pharmacology; D008288:Malaria / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D010720:Phosphines / Q000737:chemistry / Q000494:pharmacology; D010962:Plasmodium berghei / Q000378:metabolism*; D012834:Silver / Q000737:chemistry / Q000494:pharmacology
D000962:Antimalarials; D056831:Coordination Complexes; D010720:Phosphines; D012834:Silver; D006046:Gold; D003300:Copper; C044646:phosphine
Antimalarials; Copper(I); Gold(I); Phosphane complexes; Silver(I); Transmission blocking