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Synthesis and Antileishmanial Evaluation of N-Phenyl-2-phenoxyacetamides Derived from Carvacrol

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Leishmaniasis, caused by protozoa of the genus Leishmania and transmitted by sandflies, remains prevalent in underdeveloped countries. The disease manifests in three clinical forms: cutaneous, mucocutaneous, and visceral, the latter being fatal without adequate treatment. Current therapies, including pentavalent antimonials, have important limitations, such as high toxicity and reduced efficacy. This study investigates synthetic compounds derived from carvacrol as potential therapeutic alternatives. Carvacrol serves as a precursor for the synthesis of carvacroxyacetic acid, a key intermediate in producing N -phenyl-2-phenoxyacetamides. Ten novel molecules were synthesized with yields ranging from 11% to 60%. All synthesized compounds were characterized using mass spectrometry, 1 H NMR and 13 C NMR. Additionally, the structure of compound 9 (C 18 H 20 FNO 2 ) was confirmed by X-ray crystallography. Cytotoxicity assays with macrophages and Vero cells revealed that all ten N -phenyl-2-phenoxyacetamides exhibited low or no toxicity at the tested concentrations. Compounds 5 and 7 demonstrated significant antileishmanial activity against Leishmania braziliensis, outperforming both the untreated control and the precursor carvacroxyacetic acid (CA). Furthermore, their efficacy against the parasite exceeded for the activity of pure carvacrol reported in the literature. These findings highlight the significant potential of these compounds and emphasize the importance of further studies to elucidate their mechanisms of action and explore broader therapeutic applications.

Source: ACS Omega

DOI: 10.1021/acsomega.4c11359