XWL-5-11

Giardiasis is a common intestinal infection caused by the parasitic protozoan Giardia intestinalis. Current treatment relies on drugs such as metronidazole, which are associated with therapeutic failure and potential toxicity, highlighting the need for new treatment strategies. Topoisomerases, enzymes involved in regulating DNA topology, represent promising targets for drug development, including treatment of protozoan infections. The present study investigated the effects of type II topoisomerase inhibitors on G. intestinalis. Trophozoites were exposed to 1, 5, 10, or 20 μM nalidixic acid, enoxacin, or norfloxacin. At 24, 48, and 72 h, proliferation, viability, cell-cycle progression, and ultrastructure of the parasites were investigated. In silico analyses were also performed. Enoxacin exhibited a moderate antiparasitic activity (IC₅₀ =13.3 μM), whereas norfloxacin showed significant effects only at a concentration of 20 μM. In contrast, nalidixic acid reduced trophozoite proliferation and viability (IC50 = 4.3 μM), leading to cell-cycle arrest at the G2/M phase. Cell rounding, the formation of autophagic-like vacuoles, and the internalization of some flagella were observed. Alpha-tubulin labeling was detected in punctate spots on the flagellar tip of treated trophozoites. Treatment of Caco-2 cells with nalidixic acid resulted in approximately 15% reduction in cell viability only at concentrations above 50 μM. In silico analysis suggested that the compounds could interact with GiTopo2 and DNA strands. These findings support the potential of topoisomerase inhibitors as promising candidates for alternative or adjunct therapies for giardiasis.