Nine promising candidates were identified with IC50 values below 10 nM against all tested species and strains, and they showed no toxicity at concentrations up to 900 µM. Both multi-drug-resistant and drug-sensitive P. falciparum strains were sensitive to the tested compounds. Among these candidates, JPC-2060 emerged as the most promising for further investigation. The goal is to improve this option by modifying and examining related treatments.
“Our study [shows] the importance of standardized culture conditions in … accurate comparisons of drug susceptibility [in] different parasitic species and strains in [Babesia].
Identifying highly potent [Babesia] … antiparasitic drugs that target DHFR-TS enzymes represents a significant advancement in the quest for effective treatments against malaria and babesiosis.
Using DFS20, a culture medium that provides uniform nutrient supplementation, including essential elements such as putrescine, linoleic acid, and lipoic acid crucial for the growth of B. duncani. By utilizing DFS20 as a standardized culture medium for culturing B. duncani, B. divergens, B. MO1, and P. falciparum strains, we created a platform conducive to more reliable cross-species and cross-strain comparisons of drug susceptibility. Using these standardized conditions, we screened a new library of 50 dihydrotriazines and 29 biguanides against all these species. Nine promising candidates were identified
Vydyam P, Chand M, Gihaz S, Renard I, Heffernan GD, Jacobus LR, Jacobus DP, Saionz KW, Shah R, Shieh H-M, Terpinski J, Zhao W, Cornillot E, Ben Mamoun C. In vitro efficacy of next-generation dihydrotriazines and biguanides against babesiosis and malaria parasites. Antimicrob Agents Chemother. 2024 Sep 4;68(9):e0042324. doi: 10.1128/aac.00423-24. Epub 2024 Aug 13. PMID: 39136469; PMCID: PMC11373198.