2026-06-08T11:04:09Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/731852024-04-09T13:51:34Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc Ramseier, Jessica author Imhof, Dennis author Hänggeli, Kai Pascal Alexander author Anghel, Nicoleta author Boubaker, Ghalia author Beteck, Richard M. author Ortega Mora, Luis Miguel author Haynes, Richard K. author Hemphill, Andrew author 2023-03-13 The effects of decoquinate (DCQ) and three O-quinoline-carbamate-derivatives were investigated using human foreskin fibroblasts (HFF) infected with Neospora caninum tachyzoites. These compounds exhibited half-maximal proliferation inhibition (IC50s) from 1.7 (RMB060) to 60 nM (RMB055). Conversely, when applied at 5 (DCQ, RMB054) or 10µM (RMB055, RMB060), HFF viability was not affected. Treatments of infected cell cultures at 0.5µM altered the ultrastructure of the parasite mitochondrion and cytoplasm within 24 h, most pronounced for RMB060, and DCQ, RMB054 and RMB060 did not impair the viability of splenocytes from naïve mice. Long-term treatments of N. caninum-infected HFF monolayers with 0.5µM of each compound showed that only exposure to RMB060 over a period of six consecutive days had a parasiticidal effect, while the other compounds were not able to kill all tachyzoites in vitro. Thus, DCQ and RMB060 were comparatively assessed in the pregnant neosporosis mouse model. The oral application of these compounds suspended in corn oil at 10 mg/kg/day for 5 d resulted in a decreased fertility rate and litter size in the DCQ group, whereas reproductive parameters were not altered by RMB060 treatment. However, both compounds failed to protect mice from cerebral infection and did not prevent vertical transmission/pup mortality. Thus, despite the promising in vitro efficacy and safety characteristics of DCQ and DCQ-derivatives, proof of concept for activity against neosporosis could not be demonstrated in the murine model. 2076-0817 10.3390/pathogens12030447 https://hdl.handle.net/20.500.14352/73185 https://doi.org/10.3390/pathogens12030447 https://www.mdpi.com/2076-0817/12/3/447 In Vitro versus in Mice: Efficacy and Safety of Decoquinate and Quinoline-O-Carbamate Derivatives against Experimental Infection with Neospora caninum Tachyzoites