Synergistic in-vitro activity of Fosinopril alone and in combination with imidocarb dipropionate against Babesia bovis

Résumé fourni par la source

Bovine babesiosis, caused by Babesia bovis is a major cattle disease worldwide, particularly in tropical and subtropical regions. A commonly used drug for the control and treatment of babesiosis is imidocarb dipropionate (ID), which has proved effective against B. bovis . Nevertheless, its toxicity to ruminants and other mammals, along with the persistence of drug residues in meat and milk for several months after treatment, has led to restriction on its use. Furthermore, several reports indicate that complete parasite elimination is not obtained in some cases. Interestingly, the angiotensin-converting enzyme (ACE) inhibitor Fosinopril has been recently found to exhibit potent antibabesial activity against Babesia duncani . In this study, we investigated the in-vitro activity of Fosinopril alone and in fixed-ratio combinations with ID against the B. bovis Texas T2Bo isolate. Quantitative dose–response analyses of the in-vitro activity showed that Fosinopril exhibited measurable activity against the Babesia bovis T2Bo isolate, with an IC 50 value of 541.2 nM, whereas ID demonstrated greater potency, with an IC 50 value of 124.3 nM. When fixed-ratio combination studies were conducted to evaluate interactions between two drugs, the low-dose regimen Comb-4 (108 nM Fosinopril + 25 nM ID) was the only tested combination that met the predefined ΣFIC criterion for synergy (ΣFIC = 0.40). MDBK cells viability testing showed that ID reduced cell viability at the parasite-relevant concentration tested, whereas Fosinopril and the low-dose combination treatments maintained high MDBK cell viability under the same in-vitro screening conditions. Overall, these proof-of-concept in-vitro findings suggest that Fosinopril has potential as a repurposed therapeutic agent for the treatment of B. bovis -infection in cattle. Low-dose Fosinopril–ID combinations may provide a dose-sparing direction for future pharmacological studies.

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