Anti-amoebic activity of acyclic and cyclic-samarium complexes on Acanthamoeba

Eny Kusrini, Fatimah Hashim, Cindy Gunawan, Riti Mann, Wan Nor Nadhirah Wan Noor Azmi, Nakisah Mat Amin

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

This work investigated the anti-amoebic activity of two samarium (Sm) complexes, the acyclic complex [bis(picrato)(pentaethylene glycol)samarium(III)] picrate—referred to as [Sm(Pic)2(EO5)](Pic)—and the cyclic complex [bis(picrato)(18-crown-6)samarium(III)] picrate—referred to as [Sm(Pic)2(18C6)](Pic). Both Sm complexes caused morphological transformation of the protozoa Acanthamoeba from its native trophozoite form carrying a spine-like structure called acanthopodia, to round-shaped cells with loss of the acanthopodia structure, a trademark response to environmental stress. Further investigation, however, revealed that the two forms of the Sm complexes exerted unique cytotoxicity characteristics. Firstly, the IC50 of the acyclic complex (0.7 μg/mL) was ~ 10-fold lower than IC50 of the cyclic Sm complex (6.5 μg/mL). Secondly, treatment of the Acanthamoeba with the acyclic complex caused apoptosis of the treated cells, while the treatment with the cyclic complex caused necrosis evident by the leakage of the cell membrane. Both treatments induced DNA damage in Acanthamoeba. Finally, a molecular docking simulation revealed the potential capability of the acyclic complex to form hydrogen bonds with profilin—a membrane protein present in eukaryotes, including Acanthamoeba, that plays important roles in the formation and degradation of actin cytoskeleton. Not found for the cyclic complex, such potential interactions could be the underlying reason, at least in part, for the much higher cytotoxicity of the acyclic complex and also possibly, for the observed differences in the cytotoxicity traits. Nonetheless, with IC50 values of < 10 μg/mL, both the acyclic and cyclic Sm complexes feature a promising potential as cytotoxic agents to fight amoebic infections.

Original languageEnglish
Pages (from-to)1409-1417
Number of pages9
JournalParasitology Research
Volume117
Issue number5
DOIs
Publication statusPublished - 1 May 2018

Keywords

  • Acyclic and cyclic structures
  • Anti-amoebic
  • Apoptosis
  • Necrosis
  • Profilin
  • Samarium complexes

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