In vitro antifilarial activity of organometallic complexes against infective larvae of Molinema dessetae and adult females of Brugia pahangi.
New organometallic complexes having protozoocidal properties were evaluated for their in vitro antifilarial activity using two models: infective larvae of Molinema dessetae and adult females of Brugia pahangi. The compound most active on the M. dessetae model was Ir(I)-COD-pentamidine tetraphenylborate with an EC50 = 6 +/- 1 microM after 7-day-incubation. In the 2-aminobenzothiazole series, Ruthenium was more potent than Iridium for antifilarial activity. A dithiocarbamate function significantly enhanced the antifilarial activity. The compounds derived from benzimidazole were inactive whatever the metal (Iridium or Rhodium). The other compounds exhibited EC50 ranging from 10 to 31 microM. On adult female Brugia pahangi in vitro, Pt-DDH-N-acetylleucine, Pt-diminazene and Pd-Cl4-piperazine at 20 microM began to kill both microfilariae and the developing embryos within the mothers on day 2. The compounds, except for Pd-Cl4-piperazine, killed the adults after 5 days. Rh-Cl-2-chloropyridine caused obvious slowing of the adults from day 3 onward but did not affect the viability of adults, microfilariae or developing embryos. In vivo antifilarial investigations are necessary to appreciate the real advantage of heavy metal complexes in the experimental treatment of filariasis.
Faculté de Pharmacie, Université de Paris-Sud, Châtenay-Malabry, France.
P M
PM
Loiseau
J J
JJ
Jaffe
D G
DG
Craciunescu
D000818:Animals; D017179:Brugia pahangi / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D005369:Filaricides / Q000494:pharmacology*; D005370:Filarioidea / Q000187:drug effects*; D007814:Larva / Q000187:drug effects*; D009942:Organometallic Compounds / Q000494:pharmacology*; D013997:Time Factors
D005369:Filaricides; D009942:Organometallic Compounds