Riluzole, a Derivative of Benzothiazole as a Potential Anti-Amoebic Agent against Entamoeba histolytica

Abstract

Amoebiasis is produced by the parasite Entamoeba histolytica; this disease affects millions of people throughout the world who may suffer from amoebic colitis or amoebic liver abscess. Metronidazole is used to treat this protozoan, but it causes important adverse effects that limit its use. Studies have shown that riluzole has demonstrated activity against some parasites. Thus, the present study aimed, for the first time, to demonstrate the in vitro and in silico anti-amoebic activity of riluzole. In vitro, the results of Entamoeba histolytica trophozoites treated with IC50 (319.5 μM) of riluzole for 5 h showed (i) a decrease of 48.1% in amoeba viability, (ii) ultrastructural changes such as a loss of plasma membrane continuity and alterations in the nuclei followed by lysis, (iii) apoptosis-like cell death, (iv) the triggering of the production of reactive oxygen species and nitric oxide, and (v) the downregulation of amoebic antioxidant enzyme gene expression. Interestingly, docking studies have indicated that riluzole presented a higher affinity than metronidazole for the antioxidant enzymes thioredoxin, thioredoxin reductase, rubrerythrin, and peroxiredoxin of Entamoeba histolytica, which are considered as possible candidates of molecular targets. Our results suggest that riluzole could be an alternative treatment against Entamoeba histolytica. Future studies should be conducted to analyze the in vivo riluzole anti-amoebic effect on the resolution of amebic liver abscess in a susceptible model, as this will contribute to developing new therapeutic agents with anti-amoebic activity.

Efficacy of Paromomycin-Conjugated Nano Chitosan in Treating Entamoeba histolytica Infection in Mice

“…histolytica represented in herbal extracts, Derivative of Benzothiazole (Sohni et al, 1995;Cimanga et al, 2006;Velásquez-Torres et al, 2023;Ranasinghe et al, 2023;Nsangou et al, 2023).…”

Recent Updates on Multifunctional Nanomaterials as Antipathogens in Humans and Livestock: Classification, Application, Mode of Action, and Challenges

“…Antiparasitic drugs can impact vital parasitic functions, hindering enzymes, blocking metabolic routes, depleting vital ions, and inhibiting immune defenses, ultimately causing parasite death. Khadragy and colleagues [205] found that biosynthesized Ag-NPs effectively combat Leishmania major infection, reducing cutaneous lesions and enhancing antioxidant enzyme activities in animals. In another instance, Torres et al [206] documented metronidazole and riluzole to treat Entamoeba histolytica, causing DNA degradation, neurotransmitter interference, protozoan disintegration, nitric oxide generation, and parasitic cell death.…”

Antimalarial activities of benzothiazole analogs: A systematic review

“…Among these heterocyclic compounds, those with oxygen, sulfur, and nitrogen have the most potential as different biological pathways. Based on the chemical moiety, benzothiazole compounds have been used previously as novel interventions for different conditions such as antibiotics [19–21], anti‐tumor [22], anti‐tubercular [23–25], anti‐inflammatory [26], anti‐convulsant, imaging agent [27], glucose‐controlling, muscarinic receptor agonist, immunomodulatory and neuroprotective, anti‐Parkinson [28], antiparasitic [29], analgesics [26], and anti‐amoebic [30]. Benzothiazole is a basic natural compound that consists of fused membered rings containing heterocycles bearing thiazole as a central moiety [31].…”