Purine derivatives as potential agents against Chagas disease: Ex vivo, in vitro, in silico evaluation, and identification of targets in Trypanosoma cruzi

= 13.5 and 19.6 µM, respectively), which was more closely aligned with trypanocidal activity. In addition, 9i and 9t did not bind to TcBDF3, indicating selectivity among these targets. Molecular docking and 200 ns molecular dynamics simulations supported the stable binding of purine 9i to the TcBDF2 bromodomain pocket. In addition, purines 9i, 9j, 9m, and 9t were predicted to have good pharmacokinetic profiles for oral administration of the drug. Overall, trisubstituted purines emerged as promising antichagasic leads, with TcBDF2 engagement appearing more consistent with the observed trypanocidal activity, thereby guiding future optimisation towards a balance of potency, selectivity, and cytotoxicity.