f Acanthamoeba is an opportunistic pathogen in humans, whose infections most commonly manifest as Acanthamoeba keratitis or, more rarely, granulomatous amoebic encephalitis. Although there are many therapeutic options for the treatment of Acanthamoeba, they are generally lengthy and/or have limited efficacy. Therefore, there is a requirement for the identification, validation, and development of novel therapeutic targets against these pathogens. Recently, RNA interference (RNAi) has been widely used for these validation purposes and has proven to be a powerful tool for Acanthamoeba therapeutics. Ergosterol is one of the major sterols in the membrane of Acanthamoeba. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is an enzyme that catalyzes the conversion of HMG-CoA to mevalonate, one of the precursors for the production of cholesterol in humans and ergosterol in plants, fungi, and protozoa. Statins are compounds which inhibit this enzyme and so are promising as chemotherapeutics. In order to validate whether this enzyme could be an interesting therapeutic target in Acanthamoeba, small interfering RNAs (siRNAs) against HMG-CoA were developed and used to evaluate the effects induced by the inhibition of Acanthamoeba HMG-CoA. It was found that HMG-CoA is a potential drug target in these pathogenic free-living amoebae, and various statins were evaluated in vitro against three clinical strains of Acanthamoeba by using a colorimetric assay, showing important activities against the tested strains. We conclude that the targeting of HMG-CoA and Acanthamoeba treatment using statins is a novel powerful treatment option against Acanthamoeba species in human disease.

Focused on our interest to develop novel antiparasistic agents, the present study was aimed to evaluate the biological activity of an extract of Laurencia johnstonii collected in Baja California Sur, Mexico, against an Acantamoeba castellanii Neff strain. Bioassay-guided fractionation allowed us to identify the amoebicidal diastereoisomers α-bromocuparane (4) and α-isobromocuparane (5). Furthermore, bromination of the inactive laurinterol (1) and isolaurinterol (2) yielded four halogenated derivatives, (6)–(9), which improved the activity of the natural sesquiterpenes. Among them, the most active compound was 3α-bromojohnstane (7), a sesquiterpene derivative which possesses a novel carbon skeleton johnstane.

Primary amoebic encephalitis (PAM) is a lethal disease caused by the opportunistic pathogen, Naegleria fowleri. This amoebic species is able to live freely in warm aquatic habitats and to infect children and young adults when they perform risk activities in these water bodies such as swimming or splashing. Besides the need to increase awareness of PAM which will allow an early diagnosis, the development of fully effective therapeutic agents is needed. Current treatment options are amphotericin B and miltefosine which are not fully effective and also present toxicity issues. In this study, the in vitro activity of various sesquiterpenes isolated from the red alga Laurencia johnstonii were tested against the trophozoite stage of a strain of Naegleria fowleri. Moreover, the induced effects (apoptotic cell death) of the most active compound, laurinterol (1), was evaluated by measuring DNA condensation, damages at the mitochondrial level, cell membrane disruption and production of reactive oxygen species (ROS). The obtained results demonstrated that laurinterol was able to eliminate the amoebae at concentrations of 13.42 ± 2.57 µM and also to induced programmed cell death (PCD) in the treated amoebae. Moreover, since ATP levels were highly affected and laurinterol has been previously reported as an inhibitor of the Na+/K+-ATPase sodium–potassium ion pump, comparison with known inhibitors of ATPases were carried out. Our results points out that laurinterol was able to inhibit ENA ATPase pump at concentrations 100 times lower than furosemide.

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According to the World Health Organization, leishmaniasis is considered as a major neglected tropical disease causing an enormous impact on global public health. Available treatments were complicated due to the high resistance, toxicity, and high cost. Therefore, the search for novel sources of anti-leishmania agents is an urgent need. In the present study, an in vitro evaluation of the leishmanicidal activity of the essential oil of Tunisian chamomile (Matricaria recutita L.) was carried out. Chamomile essential oil exhibits a good activity on promastigotes forms of L. amazonensis and L. infantum with a low inhibitory concentration at 50% (IC) (10.8 ± 1.4 and 10.4 ± 0.6 μg/mL, respectively). Bio-guided fractionation was developed and led to the identification of (-)-α-bisabolol as the most active molecule with low IC (16.0 ± 1.2 and 9.5 ± 0.1 μg/mL for L. amazonensis and L. infantum, respectively). This isolated sesquiterpene alcohol was studied for its activity on amastigotes forms (IC = 5.9 ± 1.2 and 4.8 ± 1.3 μg/mL, respectively) and its cytotoxicity (selectivity indexes (SI) were 5.4 and 6.6, respectively). The obtained results showed that (-)-α-bisabolol was able to activate a programmed cell death process in the promastigote stage of the parasite. It causes phosphatidylserine externalization and membrane damage. Moreover, it decreases the mitochondrial membrane potential and total ATP levels. These results highlight the potential use of (-)-α-bisabolol against both L. amazonensis and L. infantum, and further studies should be undertaken to establish it as novel leishmanicidal therapeutic agents.