Nifuroxazide and 4-Hydroxybenzhydrazone Derivatives as New Antiparasitic ( and ) and Anti- Agents.

Nifuroxazide (Nfz) is a drug that has been used as a scaffold for designing antimicrobial and antiparasitic agents. This study aimed to synthesize and evaluate in vitro of Nfz and twenty-five 4-hydroxybenzhydrazone derivatives as potential anti-, anti-, and anti- agents. The compounds were synthesized by condensing 4-hydroxybenzhydrazide with appropriate aldehydes in acidic conditions and structurally confirmed by spectroscopic techniques. All compounds were evaluated in vitro against strains (NINOA and A1), (M379 and FCQEPS strains), and (H37Rv strain), followed by enzymatic assays against cysteine proteases. Compound (IC = 6.8 μM) had better trypanocidal activity than the reference drugs benznidazole (IC > 30 μM) and nifurtimox (IC > 7 μM) against the NINOA strain, and (IC = 7.2 μM) was the compound most active against the A1 strain with a high inhibition of cysteine proteases (IC = 4.6 μM) and low cytotoxic effects (CC >100 μM). On the other hand, compound (IC = 5.2 μM) had a 25-fold better leishmanicidal effect than glucantime (IC > 125 μM) against the M379 strain, and compound had the best leishmanicidal effects (IC = 10.2 μM) against the FCQEPS strain. Finally, , , and had minimum inhibitory concentration (MIC) values of 12.3, 5.1, and 18.8 μg/mL against , respectively. In summary, these results suggest that the compounds , , , , , , , and are candidates for further studies to develop new and more potent anti-, anti-leishmaniasis, and anti- agents.