01911nas a2200253   4500000000100000008004100001260003600042100001800078700001900096700001500115700001800130700001400148700001800162700001200180700001700192700001500209700001700224700001500241700001300256245013800269856004600407520117900453022002501632       2025                            d  bAmerican Chemical Society (ACS)1 aPrada Gori DN1 aBarrionuevo EM1 aAlberca LN1 aSbaraglini ML1 aLlanos MA1 aGiovannuzzi S1 aCarta F1 aMarchetto MI1 aSupuran CT1 aAlba Soto CD1 aGavernet L1 aTalevi A00aDiscovery of <i>Trypanosoma cruzi</i> Carbonic Anhydrase Inhibitors by a Combination of Ligand- and Structure-Based Virtual Screening  uhttps://pubmed.ncbi.nlm.nih.gov/40353317/3 a<p><em>Trypanosoma cruzi</em>&nbsp;carbonic anhydrase (<em>Tc</em>CA) has emerged as a promising therapeutic target for the treatment of Chagas disease. In this study, a sequential virtual screening strategy was employed to identify potential&nbsp;<em>Tc</em>CA inhibitors. The workflow consisted of ligand-based virtual screening applied to diverse chemical libraries, followed by target-based molecular docking to refine the selection of compounds. Six candidates were selected for their&nbsp;<em>in vitro</em>&nbsp;evaluation against both the enzyme and the parasite. All of them confirmed inhibitory activity against&nbsp;<em>Tc</em>CA, with three exhibiting&nbsp;<em>K</em><sub>i</sub>s in the nanomolar or submicromolar range. Among these, Nitrofurantoin demonstrated significant inhibitory activity, with a&nbsp;<em>K</em><sub>i</sub>&nbsp;of 93 nM against&nbsp;<em>Tc</em>CA and EC<sub>50</sub>&nbsp;of 14.82 μM against&nbsp;<em>T. cruzi</em>&nbsp;trypomastigotes. These findings suggest that Nitrofurantoin is a promising lead compound for further optimization and highlight the therapeutic potential of&nbsp;<em>Tc</em>CA as a drug target in Chagas disease.</p>
  a1549-9596, 1549-960X