The cytotoxicity study of praziquantel enantiomers

Abstract

Praziquantel (PZQ) is prescribed as a racemic mixture (racemic-PZQ, rac-PZQ), which is composed of (R)-PZQ and (S)-PZQ. In this work, the cytotoxicity of rac-PZQ and its two enantiomers (R)-PZQ and (S)-PZQ on eight cell lines (L-02, HepG2, prf-plc-5, SH-SY5Y, HUVEC, A549, HCT-15, Raw264.7) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphe-nyltetrazolium bromide and lactate dehydrogenase assays. The morphology of apoptotic cells was studied by fluorescence microscope using Hoechst 33342 staining, and the cytotoxicity of the compounds was also tested by lactate dehydrogenase assay. Results revealed that (R)-PZQ had negligible cytotoxicity against L-02, SH-SY5Y, HUVEC, A549, HCT-15, and Raw264.7 cells but selectively inhibited tumor cell lines (prf-plc-5 and HepG2). However, in contrast to (R)-PZQ, the (S)-isomer showed higher cytotoxicity against L-02 cells and lower inhibition on prf-plc-5 and HepG2 cells. Besides, (R)-PZQ showed lower cytotoxicity on SH-SY5Y cells than (S)-PZQ. Meanwhile, (R)-PZQ at <80 μM concentration could promote proliferation of macrophage cells (Raw264.7). Our research revealed that (R)-PZQ has lower cytotoxicity than (S)-PZQ and has similar cytotoxicity with rac-PZQ. (S)-PZQ is the principal enantiomer to cause side effects on human definitive hosts. These findings gave the reasonable reasons for World Health Organization to produce (R)-PZQ as a replacement for rac-PZQ for the treatment of schistosomiasis.

Albendazole and Praziquantel: Review and Safety Monitoring in Korea

“…PZQT is a pyrazinoisoquinoline with the chemical name 2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydropyrazino (2, 1-a) isoquinolin-4-one ( Fig. 3 ) [ 25 ]. PZQT is a broad spectrum anthelmintic in use since 1980, with activity against trematode or cestode helminthic infections of human and veterinary origin.…”

“…PZQT is a racemic mixture consisting of two enantiomers, R - and S -PZQT. An in vitro study showed that R -PZQT is essentially a vermicide agent with low toxicity, whereas S -PZQT has little anthelmintic activity, and induces toxicity [ 25 ]. The antischistosoma activity of R -PZQT is greater than that of S -PZQT, and its main metabolite, trans -4-OH-PZQT, is also effective against Schistosoma haematobium .…”

Slow-release praziquantel for dogs: presentation of a new formulation for echinococcosis control

“…In this study, the highest PZQ concentrations were reached 2 h after administration of 100 mg/kg PZQ using in situ slow-release preparation with R-PZQ still at 13 ng/ml after 6 months. Anti-schistosomal activity of PZQ was not only related to C max but also to the duration of exposure [ 35 ], and exposure of tapeworms to high drug concentrations and/or long time was essential for adequate treatment [ 51 , 52 ]. The mortality rate and lethal concentration of racemic PZQ on Echinococcus adult worms in vitro, was found to be 17.77 ng/ml, which meant that IC 50 of R-PZQ was 8.89 ng/ml [ 53 ].…”

Alkoxyamines Designed as Potential Drugs against Plasmodium and Schistosoma Parasites

“… 1 n = 1; 2 n = 2; 3 ND = not determined; 4 selectivity indexes are calculated as the ratio-cytotoxicity/activity on Plasmodium . As the activity on Schistosoma was based on a single dose treatment at 100 µg/mL, results are reported by a mean survival time, hence the selectivity index on Schistosoma cannot be calculated; 5 data from Reference [ 34 ]; 6 F32-ART5 is artemisinin-resistant and F32-TEM is artemisinin-sensitive. However, as artemisinin resistance is a quiescence-based phenomenon [ 35 ], these strains cannot be segregated by standard assays based on parasite proliferation.…”