Neuroleptic Drug Targets a Brain-Eating Amoeba: Effects of Promethazine on Neurotropic Acanthamoeba castellanii.

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Baig AM, Katyara P, Rajabali MN, Khaleeq A, Nazim F, Lalani S

Neuroleptic Drug Targets a Brain-Eating Amoeba: Effects of Promethazine on Neurotropic Acanthamoeba castellanii.

ACS Chem Neurosci. 2019 Jun 19;10(6):2868-2876. doi: 10.1021/acschemneuro.9b00100. Epub 2019 May 15.

PubMed ID

30977998 [ View in PubMed

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Abstract

Acanthamoeba spp. has recently been reported to express diverse group of ion channels and receptors that are expressed by human cells which bind drugs that are used in noninfectious diseases. Bioinformatics computational tools, growth assays, and 3D structural modeling have enabled the discovery of primitive muscarinic receptors, voltage-gated calcium channels, and ion transport pumps such as Na-K ATPase in this protist pathogen. The significance of the reported receptors and ion channels in the biology of Acanthamoeba is yet to be determined. We selected promethazine, which is a known antagonist of proteins like dopaminergic, histaminergic, muscarinic receptors, and calmodulin, to determine its effects on the growth and proliferation of trophozoites and cysts of Acanthamoeba spp. In order to elucidate the receptors involved in the effects produced by promethazine, we also performed individual experiments on Acanthamoeba trophozoites and cysts in the presence of the agonist of the above-mentioned receptors. Our results show that promethazine in the range of 60-100 mug/mL proved to be amoebicidal for Acanthamoeba trophozoites and at slightly higher doses ranging around 125-250 mug/mL also showed partial cysticidal effects. We also show the evidence of homology between the human targets of promethazine and similar targets in Acanthamoeba by the use of bioinformatic computational tools and 3D modeling. Promethazine and its structural analogs, because of being FDA-approved, have a wider margin of safety that can be tested as potential anti- Acanthamoeba agents in diseases like keratitis and encephalitis caused by this protist pathogen.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Promethazine	Calmodulin	Protein	Humans	Unknown	Inhibitor	Details