Anti-Toxoplasma gondii effect of lupane-type triterpenes from the bark of black alder (Alnus glutinosa) and identification of a potential target by reverse docking

Abstract

Toxoplasmosis is a worldwide parasitosis that is generally benign. The infestation may pose a risk to immunocompromized patients and to fetuses when pregnant women have recently seroconverted. Current treatments have numerous side effects and chemoresistance is emerging, hence the need to find new anti-Toxoplasma gondii substances. This study focuses on the antiparasitic potential of lupane-type pentacyclic triterpenes isolated from the bark of black alder (Alnus glutinosa), as well as the hypothesis of their macromolecular target by an original method of reverse docking. Among the isolated triterpenes, betulone was the most active compound with an IC50 of 2.7 ± 1.2 μM, a CC50 greater than 80 μM, and a selectivity index of over 29.6. An additional study of the anti-T. gondii potential of commercially available compounds (betulonic acid methyl ester and betulonic acid) showed the important role of the C3 ketone function and the C28 oxidation level on the lupane-type triterpene in the antiparasitic activity since their IC50 and CC50 were similar to that of betulone. Finally, the most active compounds were subjected to the AMIDE reverse docking workflow. A dataset of 87 T. gondii proteins from the Protein Data Bank was created. It identified calcium-dependent protein kinase CDPK3 as the most likely target of betulin derivatives.

Evaluation of the Anti-Toxoplasma gondii Efficacy, Cytotoxicity, and GC/MS Profile of Pleopeltis crassinervata Active Subfractions

“…Commercially available triterpenes, such as betulin, betulinic acid, and betulone, have been shown to inhibit the growth of T. gondii RH tachyzoites with inhibition rates of 44%, 49%, and 99% at 10 mM, respectively. The n-heptane extract of Alnus glutinosa exhibited significant toxoplasmicidal activity without cytotoxicity and with an IC 50 of 25.08 mg/mL and a selectivity index of 3.99; the major constituents of this extract were triterpenes [41]. Lupane-type triterpenoids extracted from the bark of black Alnus glutinosa exhibited in vitro anti-Toxoplasma (RH strain) activity.…”

Anti-Toxoplasma gondii screening of eight species and bio-guided identification of metabolites of Elaeis guineensis leaves, a preliminary study

“…The IC 50 assays were processed in the same conditions as previously described (21) Each experiment was performed with three controls: control with host cells alone, control with host cells and parasites without the drug for parasite multiplication, and control with host cells with parasites and pyrimethamine at 1 μM. The intensity of the staining is proportional to the amount of parasites present in the well.…”

Advanced high-resolution chromatographic strategies for efficient isolation of natural products from complex biological matrices: from metabolite profiling to pure chemical entities

“…MPLC and FC are operated with usually with 15-30 lm stationary phase particles (pressure: tens of bars) and semi-preparative HPLC with 5-10 lm particles (pressure: hundreds of bars) (Atanasov et al 2015;Bucar et al 2013;Sticher 2008). Semi-preparative HPLC has been mainly used for the final purification step of simplified fractions originating from the other preparative approaches (Angelis et al 2020;Darme et al 2022;Human et al 2021;Jing et al 2022;Keller et al 2021;Zhou et al 2022).…”