In Vitro Evaluation of p-Toluenesulfonyl Hydrazones as Anti-Trypanosoma cruzi and Leishmanicidal Agents

Introduction: Neglected tropical diseases (NTDs), such as Chagas disease (CD) and Cutaneous Leishmaniasis (CL), are significant global health concerns. The limited number of treatments and their severe adverse effects worsen the situation. Therefore, the development of molecules as a new pharmacological alternative is necessary. This work aimed to obtain new p- Toluenesulfonyl hydrazones derivatives to determine their potential antiparasitic activity against Trypanosoma cruzi (T. cruzi) and Leishmania mexicana (L. mexicana). Methods: Compounds were synthesized by condensing p-Toluenesulfonyl hydrazide with aromatic aldehydes using acetic acid as a catalyst. All compounds were structurally elucidated using infrared (IR) spectroscopy, proton and carbon nuclear magnetic resonance (¹H and ¹³C NMR), and Ultra-Performance Liquid Chromatography-tandem Mass Spectrometry (UPLCMS). The Queretaro (Qro) strain of T. cruzi and the M379 strain of L. mexicana were used for in vitro assays. Results: Compound pT-21 (IC50= 49.6 μM) was the most active agent against the T. cruzi Qro strain. Meanwhile, compounds pT-15 and pT-21 inhibited the proliferation of L. mexicana promastigotes with an IC50 value of 59.2 and 13.8 μM, respectively. In addition, these compounds had low cytotoxic effects against Vero cell lines (CC50 values >100 μM). Discussion: In this study, compound pT-21 inhibited the proliferation of T. cruzi and L. mexicana in vitro. Its activity is attributed to the reactivity of the 5-nitrofuran ring (present in other drugs such as nifurtimox). Future research could focus on identifying the pharmacological target of compound pT-21 to facilitate rational drug design and enhance its potency against these parasites. Conclusion: In summary, these results show that p-Toluenesulfonyl hydrazones serve as a scaffold to aid in the development of potent and selective agents against T. cruzi and L. mexicana.