Anti-trypanosomatid activity of platinum–sterol hydrazone imidazoline complexes

Abstract

In the search for effective and less toxic drugs against Leishmania mexicana and Trypanosoma cruzi parasites, two new complexes trans-[Pt(Him1) 2 (Cl) 2 ] (1) and trans-[Pt(Him2) 2 (Cl) 2 ] (2) were synthesized by the reactions of K 2 PtCl 4 with sterol hydrazone ligands 20-hydrazone-imidazoline-2-yl-5a-pregnan-3b-ol (Him1) and 22-hydrazoneimidazoline-2-yl-chol-5-ene-3b-ol (Him2). The complexes were characterized by a combination of physicochemical and spectroscopic methods. The ligands and their platinum complexes were evaluated in vitro against promastigotes of L. mexicana and epimastigotes of T. cruzi. Both the free sterol hydrazones and their platinum complexes at 10 lM final concentration induced a potent leishmanicidal activity (LD 100 B 48 h). Trypanostatic effect (IC 50 B 72 h) was observed with Him1, trans-[Pt(Him1) 2 (Cl) 2 ] (1) and trans-[Pt(Him2) 2 (Cl) 2 ] (2), but at 5 lM concentration for the latter. Free Him2 at 5 lM concentration proved to be a potent trypanocidal agent (LD 50 , 24 h), reaching LD 100 after 72 h of exposure. Additionally, Him2 and its platinum derivative when tested against human lymphocytes at twice the antiTrypanosoma effective concentration did not show cytotoxicity. These findings demonstrate the potent anti-trypanosomatid activity of these sterol hydrazone imidazolines and their platinum complexes, and especially the low cytotoxicity of Him2 and trans-[Pt(Him2) 2 (Cl) 2 ] against human immunocompetent cells.

Metal–azasterol complexes: Synthesis, characterization, interaction studies with DNA and TrxR and Biological Evaluation

“…Recently, we reported the synthesis of platinum-sterol hydrazone complexes and their activities as anti-trypanosomatid [21]. The 24-SMT inhibitors used as ligands were 20-hydrazone-imidazoline-2-yl-5α-pregnan-3β-ol (H1) and 22-hydrazoneimidazoline-2-yl-chol-5-ene-3β-ol (H3 mentioned above).…”