Synthesis and Antitrypanosomal Activity of Novel 2-Nitroimidazole-3,5-Disubstituted Isoxazole Derivatives with Diaryl Ether and Thioether Substituents
In this study, we synthesized 17 novel 2-nitroimidazole-3,5-disubstituted isoxazole analogs of benznidazole with diaryl ether and thioether substituents and evaluated their antitrypanosomal activity and cytotoxicity. Compounds <b>6a</b>-<b>q</b> were obtained in moderate-to-good yields (29-81%). Derivatives <b>6a</b>-<b>g</b> displayed greater activity than benznidazole. <b>6b</b> (<i>R</i> = Ph-O-(4-F-Ph)) and <b>6g</b> (<i>R</i> = Ph-O-(4-OCH<sub>3</sub>-Ph)) were the most active of all the synthesized compounds (IC<sub>50</sub> = 0.50 μM and IC<sub>50</sub> = 0.64 μM, respectively). Compounds <b>6h</b>-<b>n</b> included a 3-fluoro substituent in the first phenyl ring, resulting in lower activity. The diaryl thioether compounds <b>6o</b>-<b>q</b> exhibited lower anti-<i>T. cruzi</i> activity than diarylether analogs.
Authors
- Cristiane Y. Kawasoko (ORCID: https://orcid.org/0000-0002-3515-3272)
- Saulo Euclides Silva-Filho (ORCID: https://orcid.org/0000-0002-9676-7622)
- Larissa B. B. Santos
- Adriano C. M. Baroni (ORCID: https://orcid.org/0000-0002-5371-3755)
- Diego B. Carvalho (ORCID: https://orcid.org/0000-0002-9867-5094)
- Gisele Bulhões Portapilla (ORCID: https://orcid.org/0000-0003-0195-9822)
- Sérgio de Albuquerque (ORCID: https://orcid.org/0000-0003-2530-9226)
- Talícia S. Silva
- Palimécio G. Guerrero
- Omar Dias Lacerda
Institutions
- Universidade Federal de Mato Grosso do Sul (BR)
- Universidade Tecnológica Federal do Paraná (BR)
- Universidade de Ribeirão Preto (BR)
- Universidade de São Paulo (BR)
Publication Details
- Journal
- ACS Omega
- Published
- 2025-11-15
- DOI
- https://doi.org/10.1021/acsomega.5c08312
- Citations
- 1
- Primary Topic
- Trypanosoma species research and implications
- Type
- article
- Field-Weighted Citation Impact
- 1.35