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.
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Acknowledgements
The authors wish to thank the Universiti Malaysia Terengganu (UMT) for providing the Acanthamoeba. We would also like to thank Intan Nursuraya for her assistance with the in silico molecular docking calculation.
Funding
This article’s publication is partially supported by the United States Agency for International Development (USAID) through the Sustainable Higher Education Research Alliance (SHERA) Program for Universitas Indonesia’s Scientific Modeling, Application, Research and Training for City-centered Innovation and Technology Project, Grant No. AID-497-A-1600004, Sub Grant No. IIE-00000078-UI-1.
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Kusrini, E., Hashim, F., Gunawan, C. et al. Anti-amoebic activity of acyclic and cyclic-samarium complexes on Acanthamoeba. Parasitol Res 117, 1409–1417 (2018). https://doi.org/10.1007/s00436-018-5814-x
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DOI: https://doi.org/10.1007/s00436-018-5814-x